Co-reporter:Yurong Zhao, Jiqian Wang, Li Deng, Peng Zhou, Shengjie Wang, Yanting Wang, Hai Xu, and Jian R. Lu
Langmuir November 5, 2013 Volume 29(Issue 44) pp:13457-13464
Publication Date(Web):October 3, 2013
DOI:10.1021/la402441w
Peptide self-assembly is of direct relevance to protein science and bionanotechnology, but the underlying mechanism is still poorly understood. Here, we demonstrate the distinct roles of the noncovalent interactions and their impact on nanostructural templating using carefully designed hexapeptides, I2K2I2, I4K2, and KI4K. These simple variations in sequence led to drastic changes in final self-assembled structures. β-sheet hydrogen bonding was found to favor the formation of one-dimensional nanostructures, such as nanofibrils from I4K2 and nanotubes from KI4K, but the lack of evident β-sheet hydrogen bonding in the case of I2K2I2 led to no nanostructure formed. The lateral stacking and twisting of the β-sheets were well-linked to the hydrophobic and electrostatic interactions between amino acid side chains and their interplay. For I4K2, the electrostatic repulsion acted to reduce the hydrophobic attraction between β-sheets, leading to their limited lateral stacking and more twisting, and final fibrillar structures; in contrast, the repulsive force had little influence in the case of KI4K, resulting in wide ribbons that eventually developed into nanotubes. The fibrillar and tubular features were demonstrated by a combination of cryogenic transmission electron microscopy (cryo-TEM), negative-stain transmission electron microscopy (TEM), and small-angle neutron scattering (SANS). SANS also provided structural information at shorter scale lengths. All atom molecular dynamics (MD) simulations were used to suggest possible molecular arrangements within the β-sheets at the very early stage of self-assembly.
Co-reporter:Meiwen Cao, Sha Lu, Wenjing Zhao, Li Deng, Meng Wang, Jiqian Wang, Peng Zhou, Dong Wang, Hai Xu, and Jian R. Lu
ACS Applied Materials & Interfaces November 15, 2017 Volume 9(Issue 45) pp:39174-39174
Publication Date(Web):October 25, 2017
DOI:10.1021/acsami.7b11681
Six surfactant-like peptides with the same amino acid composition but different primary sequences are designed, including G3A3V3I3K3, K3I3V3A3G3, I3V3A3G3K3, K3G3A3V3I3, V3G3I3A3K3, and K3A3I3G3V3. These peptides form antiparallel β-sheets during self-assembly. Because the constituent residues have different side chain size and hydrophobicity, sequence changes adjust group distribution and hydrophobicity on the two sides of a given β-sheet. This consequently tunes the binding energy of the side-to-side pairing conformations and leads to different self-assembled structures. G3A3V3I3K3 and K3I3V3A3G3 form short nanorods with diameters of 8.5 ± 1.0 nm and lengths <150 nm. I3V3A3G3K3 and K3G3A3V3I3 form nanosheets with heights of 4.0 ± 0.5 nm and limited lengths and widths. V3G3I3A3K3 and K3A3I3G3V3 form long fibrils with diameters of 7.0 ± 1.0 nm and lengths of micrometer scale. These nanostructures exhibit different capacity in encapsulating insoluble hydrophobic drug molecules and delivering them into the cells. The nanosheets of I3V3A3G3K3 and K3G3A3V3I3 can encapsulate both nile red and doxorubicin molecules to an extent of up to 17−23% in mole ratio. Moreover, the shape and size of the nanostructures affect the drug delivery into cells greatly, with the nanosheets and short rods exhibiting higher efficiency than the long fibrils. The study provides new insights into programmed peptide self-assembly toward specific functionalities.Keywords: drug delivery; encapsulation; nanostructures; peptide self-assembly; primary sequence; β-sheet pairing;
Co-reporter:Li Deng;Peng Zhou;Yanting Wang;Jian R. Lu
Langmuir May 10, 2016 Volume 32(Issue 18) pp:4662-4672
Publication Date(Web):2017-2-22
DOI:10.1021/acs.langmuir.6b00287
To study how the conformational propensities of individual amino acid residues, primary structures (i.e., adjacent residues and molecular lengths), and intermolecular interactions of peptides affect their self-assembly properties, we report the use of replica exchange molecular dynamics (REMD) to investigate the monomers, dimers, and trimers of a series of short surfactant-like peptides (I3K, L3K, L4K, and L5K). For four-residue peptides X3K (I3K and L3K), the results show that their different aggregation behaviors arise from the different intrinsic conformational propensities of isoleucine and leucine. For LmK peptides (L3K, L4K, and L5K), the molecular length is found to dictate their aggregation via primarily modulating intermolecular interactions. Increasing the number of hydrophobic amino acid residues of LmK peptides enhances their intermolecular H-bonding and promotes the formation of β-strands in dimer and trimer aggregates, overwhelming the intrinsic preference of Leu for helical structures. Thus, the interplay between the conformational propensities of individual amino acid residues for secondary structures and molecular interactions determines the self-assembly properties of the peptides, and the competition between intramolecular and intermolecular H-bonding interactions determines the probability of β-sheet alignment of peptide molecules. These results are validated by comparing simulated and experimental CD spectra of the peptides. This study will aid the design of short peptide amphiphiles and improve the mechanistic understanding of their self-assembly behavior.
Co-reporter:Meng Wang, Peng Zhou, Jiqian Wang, Yurong Zhao, Hongchao Ma, Jian R. Lu, and Hai Xu
Journal of the American Chemical Society March 22, 2017 Volume 139(Issue 11) pp:4185-4185
Publication Date(Web):February 27, 2017
DOI:10.1021/jacs.7b00847
Peptide and protein fibrils have attracted an enormous amount of interests due to their relevance to many neurodegenerative diseases and their potential applications in nanotechnology. Although twisted fibrils are regarded as the key intermediate structures of thick fibrils or bundles of fibrils, the factors determining their twisting tendency and their handedness development from the molecular to the supramolecular level are still poorly understood. In this study, we have designed three pairs of enantiomeric short amphiphilic peptides: LI3LK and DI3DK, LI3DK and DI3LK, and LaI3LK and DaI3DK, and investigated the chirality of their self-assembled nanofibrils through the combined use of atomic force microscopy (AFM), circular dichroism (CD) spectroscopy, scanning electron microscopy (SEM), and molecular dynamic (MD) simulations. The results indicated that the twisted handedness of the supramolecular nanofibrils was dictated by the chirality of the hydrophilic Lys head at the C-terminal, while their characteristic CD signals were determined by the chirality of hydrophobic Ile residues. MD simulations delineated the handedness development from molecular chirality to supramolecular handedness by showing that the β-sheets formed by LI3LK, LaI3LK, and DI3LK exhibited a propensity to twist in a left-handed direction, while the ones of DI3DK, DaI3DK, and LI3DK in a right-handed twisting orientation.
Co-reporter:Mingxuan Du;Yong Bu;Yan Zhou;Yurong Zhao;Shengjie Wang
RSC Advances (2011-Present) 2017 vol. 7(Issue 21) pp:12711-12718
Publication Date(Web):2017/02/21
DOI:10.1039/C7RA00829E
Although many nanomaterials have been prepared in vitro by mimicking biomineralization, the biomimetic synthesis of hybrids with both well-ordered nanostructures and specific functions is still in its infancy. A short designed peptide amphiphile I3K can form uniform and stable nanofibers in aqueous solution, with a surface enriched in cationic lysine residue. In the present study, we have demonstrated that the peptide nanofibers could direct the synthesis of MnO2 nanowires under mild conditions. By varying the concentration of manganese precursors (KMnO4 and Mn(NO3)2), uniform branched MnO2/peptide hybrid nanowires with high porosity and a large specific surface area were obtained. The well-defined MnO2 hybrid nanowires showed significantly improved electrochemical supercapacitive properties relative to compact MnO2 nanowires and urchin-like MnO2 spheres. Their specific capacitance could attain a higher value of 421 F g−1 and retained about 93% of the initial capacitance after 2500 cycles at a scan rate of 5 mV s−1, and remained little changed during the process of progressively varying the current density. Furthermore, the electrode prepared from the uniform MnO2 hybrid nanowires showed an excellent reversibility and a reasonably high-rate capability during the charge/discharge process. Such a study provides a new methodology to prepare functional MnO2 nanostructures under mild conditions that can be used in electrochemical energy storage.
Co-reporter:Meiwen Cao;Wenjing Zhao;Peng Zhou;Zilong Xie;Yawei Sun
RSC Advances (2011-Present) 2017 vol. 7(Issue 7) pp:3796-3803
Publication Date(Web):2017/01/09
DOI:10.1039/C6RA26329A
A new type of conjugated molecule including T′3–(AKAE)2, T′3–(IKIE)2, and A′3–(AKAE)2 was designed by linking short peptide nucleic acid (PNA) segments with short ionic self-complementary peptide (ISCP) sequences. These short conjugates showed high hybridization affinity and specificity for λ-DNA. They can induce efficient DNA condensation at low micromole concentrations via a specific mechanism that involves the base pair recognition between DNA and the PNA segment and the self-aggregation of the bound PNA–ISCP molecules. Atomic force microscopy (AFM) and dynamic light scattering (DLS) measurements indicated that λ-DNA took an elongated conformation while it compacted into globules when interacting with the PNA–ISCP conjugates. The ethidium bromide displacement assay indicated that the PNA–ISCP conjugates induced DNA condensation in a way different from conventional cationic condensers such as polyethyleneimine (PEI) and hexadecyltrimethylammonium bromide (CTAB). The interaction between T′3–(AKAE)2 and a single chain oligonucleotide, d(A)36, was further studied and the results revealed that the PNA–ISCP conjugates bound with DNA mainly via base pairing recognition. The volume ratio of λ-DNA and the λ-DNA/PNA–ISCP globules was calculated based on AFM measurements, which was near 1 : 1, suggesting that the condensation was an intramolecular folding process for λ-DNA, which was prompted by the self-aggregation of the bound PNA–ISCP molecules.
Co-reporter:Daniela Ciumac, Richard A. Campbell, Hai Xu, Luke A. Clifton, Arwel V. Hughes, John R.P. Webster, Jian R. Lu
Colloids and Surfaces B: Biointerfaces 2017 Volume 150(Volume 150) pp:
Publication Date(Web):1 February 2017
DOI:10.1016/j.colsurfb.2016.10.043
•Effects of lipid monolayer charges on the binding of antimicrobial peptides.•Structure and composition of lipid monolayers.•Impact upon antimicrobial peptide binding.•Relevance to antimicrobial activity.Many antimicrobial peptides (AMPs) target bacterial membranes and they kill bacteria by causing structural disruptions. One of the fundamental issues however lies in the selective responses of AMPs to different cell membranes as a lack of selectivity can elicit toxic side effects to mammalian host cells. A key difference between the outer surfaces of bacterial and mammalian cells is the charge characteristics. We report a careful study of the binding of one of the representative AMPs, with the general sequence G(IIKK)4I-NH2 (G4), to the spread lipid monolayers of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and DPPG (1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (sodium salt)) mimicking the charge difference between them, using the combined measurements from Langmuir trough, Brewster angle microscopy (BAM) and neutron reflection (NR). The difference in pressure rise upon peptide addition into the subphase clearly demonstrated the different interactions arising from different lipid charge features. Morphological changes from the BAM imaging confirmed the association of the peptide into the lipid monolayers, but there was little difference between them. However, NR studies revealed that the peptide bound 4 times more onto the DPPG monolayer than onto the DPPC monolayer. Importantly, whilst the peptide could only be associated with the head groups of DPPC it was well penetrated into the entire DPPG monolayer, showing that the electrostatic interaction strengthened the hydrophobic interaction and that the combined molecular interactive processes increased the power of G4 in disrupting the charged membranes. The results are discussed in the context of general antibacterial actions as observed from other AMPs and membrane lytic actions.Download high-res image (294KB)Download full-size imageInfluence of membrane surface charges on the selective binding of antimicrobial peptide G4 (G(IIKK)4I-NH2), where DPPC stands for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and DPPG for 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (sodium salt).
Co-reporter:Cuixia Chen, Jing Hu, Cheng Yang, Yu Zhang, Fang Wang, Quanmeng Mu, Fang Pan, Hai Xu and Jian Ren Lu
Journal of Materials Chemistry A 2016 vol. 4(Issue 13) pp:2359-2368
Publication Date(Web):03 Mar 2016
DOI:10.1039/C6TB00155F
The artificially designed amphiphilic peptide G(IIKK)3I-NH2 has been shown to be highly effective at killing bacteria and inhibiting the growth of tumor cells whilst remaining benign to normal mammalian cells. Herein we report how the side chain length and branching of constituent amino acids affect these bioactivities. Two peptide groups were designed by utilizing G(IIKK)3I-NH2 as the base template. In Group 1, hydrophobic residues were replaced from Ile to Leu, Nle (norleucine), or Val. It was found that an increase in the side chain carbon number from 3 (Val) to 4 (Leu, Ile or Nle) substantially enhanced their antibacterial and antitumor activities, but different branching in the butyl side chain showed very different cytotoxicities to host mammalian cells, with the γ-branching in Leu eliciting the highest potency. Group 2 covered those cationic Lys residues which were replaced by synthetic homologues with shorter side chains, namely, Orn, Dab and Dap containing 3, 2 and 1 methylene units, respectively. The replacement did not affect their antibacterial activities much, but their anticancer activities were maximized in Orn and Dab. On the other hand, their cytotoxicities also became higher, indicating a multi-faceted role played by the cationic residues. Thus, changes in both the side chain length and branching strongly affected the amphiphilicity of the short peptides and their interactions with different membranes. This work has revealed a strong relationship among side chain structures, amphiphilicity and selective bioactivities of the short peptide amphiphiles.
Co-reporter:Meiwen Cao, Ningning Wang, Lei Wang, Yu Zhang, Yucan Chen, Zilong Xie, Zongyi Li, Elias Pambou, Ruiheng Li, Cuixia Chen, Fang Pan, Hai Xu, Jeffery Penny, John R. P. Webster and Jian R. Lu
Journal of Materials Chemistry A 2016 vol. 4(Issue 1) pp:152-161
Publication Date(Web):18 Nov 2015
DOI:10.1039/C5TB02065D
Different amphiphilic peptides were used to mediate the direct exfoliation of graphite into few-layered graphene flakes in aqueous solutions. Charge was found to be an important parameter in determining their graphite exfoliating efficiency. The anionic molecules were more favorable than the cationic ones leading to a higher efficiency. The gemini-type peptide IleIleIleCys–CysIleIleIle (I3C–CI3) exhibited the highest efficiency, which might be attributed to its specific physicochemical properties and interactions with graphene sheets. I3C–CI3 adsorbed onto the graphene surface as either monomers or self-assembled nanoaggregates. These adsorbed species increased both electrostatic and steric repulsions between the graphene/I3C–CI3 composites. More interestingly, the graphene/I3C–CI3 composites showed a reversible pH-dependent dispersion/aggregation. This behavior resulted from the pH-sensitive protonation of the peptide molecules and was rarely found in the graphene dispersions exfoliated by traditional surfactants. Moreover, the graphene/I3C–CI3 dispersion was used to fabricate free-standing macroscopic composite films that contained different nanostructures. The study expands the library of available agents for direct graphite exfoliation to produce graphene sheets. Employing peptide molecules as graphene exfoliating and stabilizing agents avoids the use of toxic reagents, which may allow fabrication of functional composite materials for biocompatible applications.
Co-reporter:Cuixia Chen, Yu Zhang, Rui Fei, Changhai Cao, Meng Wang, Jingxin Wang, Jingkun Bai, Henry Cox, Thomas Waigh, Jian R. Lu, and Hai Xu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 28) pp:17833-17841
Publication Date(Web):June 23, 2016
DOI:10.1021/acsami.6b04939
The self-assembly of short peptides is a promising route to the creation of smart biomaterials. To combine peptide self-assembly with enzymatic catalysis, we design an amphiphilic short peptide I3QGK that can self-assemble into long nanoribbons in aqueous solution. Upon addition of transglutaminase (TGase), the peptide solution undergoes a distinct sol–gel transition to form a rigid hydrogel, which shows strong shear-thinning and immediate recovery properties. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) measurements indicate the occurrence of considerable nanofibers in addition to the original nanoribbons. Liquid chromatography and mass spectrometry analyses reveal the enzymatic formation of peptide dimers from monomers through intermolecular ε-(γ-glutamyl)lysine isopeptide bonding. The dimers rapidly self-assemble into flexible and entangled nanofibers, and the coexistence of the original nanoribbons and the newly created nanofibers is responsible for hydrogelation. Factor XIII in blood is converted by thrombin to an active TGase (Factor XIIIa) during bleeding, so the peptide solution shows a more rapid and effective hemostasis via a combination of gelling blood and promoting platelet adhesion, relative to other hemostasis methods or materials. These features of I3QGK, together with its low cytotoxicity against normal mammalian cells and noninduction of nonspecific immunogenic responses, endow it with great potential for future clinical hemostasis applications.
Co-reporter:Jingkun Bai, Cuixia Chen, Jingxin Wang, Yu Zhang, Henry Cox, Jing Zhang, Yuming Wang, Jeffrey Penny, Thomas Waigh, Jian R. Lu, and Hai Xu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 24) pp:15093-15102
Publication Date(Web):May 31, 2016
DOI:10.1021/acsami.6b03770
Hydrogels offer great potential for many biomedical and technological applications. For clinical uses, hydrogels that act as scaffold materials for cell culture, regenerative medicine, and drug delivery are required to have bactericidal properties. The amphiphilic peptide A9K2 was designed to effectively inhibit bacterial growth via a mechanism of membrane permeabilization. The present study demonstrated that addition of fetal bovine serum (FBS) or plasma amine oxidase (PAO) induced a sol–gel transition in A9K2 aqueous solutions. The transformation of A9K2 molecules catalyzed by lysyl oxidase (LO) in FBS or PAO accounted for the hydrogelation. Importantly, the enzymatic A9K2 hydrogel displayed high antibacterial ability against both Gram-negative and Gram-positive bacterial strains while showing extremely low mammalian cell cytotoxicity, thus demonstrating good biocompatibility. Under established coculture conditions, the peptide hydrogel showed excellent selectivity by favoring the adherence and spreading of mammalian cells, while killing pathogenic bacteria, thus avoiding bacterial contamination. These advantages endow the enzymatic A9K2 hydrogel with great potential for biomedical applications.
Co-reporter:Cuixia Chen, Cheng Yang, Yucan Chen, Fang Wang, Quanmeng Mu, Jing Zhang, Zongyi Li, Fang Pan, Hai Xu, and Jian Ren Lu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 40) pp:26501
Publication Date(Web):September 19, 2016
DOI:10.1021/acsami.6b08297
G(IIKK)3I-NH2 has been recently shown to be highly effective at killing bacteria and inhibiting cancer cell growth while remaining benign to normal host mammalian cells. The aim of this work is to evaluate how residue substitutions of Ala (A), Val (V), Glu (E), and Lys (K) for the N-terminal Gly (G) or C-terminal Ile (I) of G(IIKK)3I-NH2 affect the physiochemical properties and bioactivity of the variants. All substitutions caused the reduction of peptide hydrophobicity, while N-terminal substitutions had a less noticeable effect on the surface activity and helix-forming ability than C-terminal substitutions. N-terminal variants held potent anticancer activity but exhibited reduced hemolytic activity; these actions were related to the maintenance of their moderate surface pressures (12–16 mN m–1), while their hydrophobicity was reduced. Thus, N-terminal substitutions enhanced the cell selectivity of the mutants relative to the control peptide G(IIKK)3I-NH2. In contrast, C-terminal variants exhibited lower anticancer activity and much lower hemolytic activity except for G(IIKK)3V-NH2. These features were correlated well with their lower surface pressures (≤10 mN m–1) and decreased hydrophobicity. In spite of its very low helical content, the C-terminal variant G(IIKK)3V-NH2 still displayed potent anticancer activity while retaining high hemolytic activity as well, again correlating well with its relatively high surface pressure and hydrophobicity. These results together indicated that surface activity governs the anticancer activity of the peptides, but hydrophobicity influences their hemolytic activity. In contrast, helicity appears to be poorly correlated to their bioactivity. This work has demonstrated that N-terminal modifications provide a useful strategy to optimize the anticancer activity of helical anticancer peptides (ACPs) against its potential toxicity to mammalian host cells.Keywords: anticancer activity; anticancer peptides; cell selectivity; helicity; hemolytic activity; hydrophobicity; surface activity; terminal substitution
Co-reporter:Peng Zhou, Li Deng, Yanting Wang, Jian R. Lu, Hai Xu
Journal of Colloid and Interface Science 2016 Volume 464() pp:219-228
Publication Date(Web):15 February 2016
DOI:10.1016/j.jcis.2015.11.030
To understand how molecular interactions lead to the self-assembly of twisted, helical and flat nanoribbons, we have compared the hierarchical self-assembly processes of three selected octapeptides with the same amino acid composition but different sequences by both experiments and molecular dynamics (MD) simulations. KE-F8 (NH2-KEFFFFKE-CONH2) and EK-F8 (NH2-KEFFFFEK-CONH2) have the same distribution of hydrophobic residues and only differ by swapping the positive and negative charged residues at their C-terminals, while KFE-8 (NH2-KFEFKFEF-CONH2) differs from KE-F8 and EK-F8 by having all hydrophobic and charged residues evenly distributed. MD simulations indicated that the competition between electrostatic and hydrophobic interactions at the molecular level results in different initial packing modes: KE-F8 monomers form completely matched anti-parallel β-sheets, EK-F8 monomers align with one residue shifting, and KFE-8 monomers pack β-sheets with two heterogeneous surfaces, consistent with previously suggested models. Driven by inter-strand and inter-sheet interactions, further growth of these molecular templates leads to larger oligomers with different twisting and stacking degrees, which are structurally consistent with the experimentally observed self-assembled morphologies. Further MD simulations showed that the competition between intra-β-sheet and inter-β-sheet interactions is responsible for the different twisting and stacking degrees of β-sheets and the subsequent formation of different nanostructures (twisted ribbons for KE-F8, helical ribbons/tubes for EK-F8 and flat ribbons for KFE-8). This study thus provided an important mechanistic insight into the fine tuning of molecular packing and interactions via peptide sequence variation leading to controllable self-assembly of twisted, helical and flat nanostructures.By tuning intra- and inter-β-sheet interactions via peptide sequence variations and their competitions, different molecular packing modes are obtained and then grow into three typical nanostructures (twisted ribbons, helical ribbons/tubes and flat ribbons).
Co-reporter:Jiqian Wang, Kai Tao, Peng Zhou, Elias Pambou, Zongyi Li, Hai Xu, Sarah Rogers, Stephen King, Jian R. Lu
Colloids and Surfaces B: Biointerfaces 2016 Volume 147() pp:116-123
Publication Date(Web):1 November 2016
DOI:10.1016/j.colsurfb.2016.07.052
•Hydrophobic interactions and steric conformation of Phes affect Aβ self-assembly.•When Phes replaced with Chas, Aβ(16–22) formed thin nanotubes morphologies.•When Phes replaced with Phgs, Aβ(16–22) formed thinner and twisted nanofibrils.•Equilibrium between lateral aggregation and twisting determines the morphologies.The effects of the two phenylalanine (Phe) residues in the blocked Aβ(16–22) peptide on its self-assembly have been investigated by replacing both of them with two cyclohexylalanines (Chas) or two phenylglycines (Phgs). TEM and SANS studies revealed that the flat and wide nanoribbons of Aβ(16–22) were transformed into thin nanotubes when replaced with Chas, and thinner and twisted nanofibrils when replaced with Phgs. The red-shifting degree of characteristic CD peaks suggested an increased twisting in the self-assembly of the derivative peptides, especially in the case of Ac-KLV(Phg)(Phg)AE-NH2. Furthermore, molecular dynamics (MD) simulations also indicated the increasing trend in twisting when Chas or Phgs were substituted for Phes. These results demonstrated that the hydrophobic interactions and spatial conformation between Cha residues were sufficient to cause lateral association of β-sheets to twisted/helical nanoribbons, which finally developed into nanotubes, while for Phg residue, the loss of the rotational freedom of the aromatic ring induced much stronger steric hindrance for the lateral stacking of Ac-KLV(Phg)(Phg)AE-NH2 β-sheets, eventually leading to the nanofibril formation. This study thus demonstrates that both the aromatic structure and the steric conformation of Phe residues are crucial in Aβ(16–22) self-assembly, especially in the significant lateral association of β-sheets.
Co-reporter:Meiwen Cao;Ningning Wang;Peng Zhou;Yawei Sun;Jiqian Wang
Science China Chemistry 2016 Volume 59( Issue 3) pp:310-315
Publication Date(Web):2016 March
DOI:10.1007/s11426-015-5495-6
A peptide nucleic acid (PNA)-peptide conjugated molecule, T′3(AKAE)2, was designed to have both a PNA segment for oligonucleotide binding and an ionic self-complementary peptide sequence for self-association. T′3(AKAE)2 could co-assemble with oligoadenines (d(A)x) to form virus-like supramolecular structures whose morphology showed dependence on the chain length and rigidity of the d(A)x molecules. Smaller nanospheres with diameters of 13.0±2.0 nm were produced in the case of d(A)6. Wormlike aggregates with lengths of 20–50 nm and diameters of 15.0±2.5 nm were found in the cases of d(A)12, d(A)18, d(A)24 and d(A)30. And larger spherical aggregates with diameters of 18±5 nm came into presence in the cases of d(A)36 and d(A)42. These nanostructures were suggested to be formed under a cooperative effect of base pair recognition and peptidic association. The study provides insights into the programmed assembly of a multi-components system as well as control of the size and shape of the co-assembled structures, which is of great significance in developing gene/drug delivery systems.
Co-reporter:Dr. Yurong Zhao;Dr. Li Deng;Wei Yang;Dr. Dong Wang;Elias Pambou;Zhiming Lu;Zongyi Li;Dr. Jiqian Wang;Dr. Stephen King;Dr. Sarah Rogers; Hai Xu; Jian R. Lu
Chemistry - A European Journal 2016 Volume 22( Issue 32) pp:11394-11404
Publication Date(Web):
DOI:10.1002/chem.201601309
Abstract
By combining experimental measurements and computer simulations, we here show that for the bola-like peptide amphiphiles XI4X, where X=K, R, and H, the hydrophilic amino acid substitutions have little effect on the β-sheet hydrogen-bonding between peptide backbones. Whereas all of the peptides self-assemble into one dimensional (1D) nanostructures with completely different morphologies, that is, nanotubes and helical nanoribbons for KI4K, flat and multilayered nanoribbons for HI4H, and twisted and bilayered nanoribbons for RI4R. These different 1D morphologies can be explained by the distinct stacking degrees and modes of the three peptide β-sheets along the x-direction (width) and the z-direction (height), which microscopically originate from the hydrogen-bonding ability of the sheets to solvent molecules and the pairing of hydrophilic amino acid side chains between β-sheet monolayers through stacking interactions and hydrogen bonding. These different 1D nanostructures have distinct surface chemistry and functions, with great potential in various applications exploiting the respective properties of these hydrophilic amino acids.
Co-reporter:Cuixia Chen, Yucan Chen, Cheng Yang, Ping Zeng, Hai Xu, Fang Pan, and Jian Ren Lu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 31) pp:17346
Publication Date(Web):July 23, 2015
DOI:10.1021/acsami.5b04547
Short designed peptide amphiphiles are attractive at killing bacteria and inhibiting cancer cell growth, and the flexibility in their structural design offers a great potential for improving their potency and biocompatibility to mammalian host cells. Amino acid sequences such as G(IIKK)nI-NH2 (n ≥ 3) have been shown to be membrane lytic, but terminal amino acid modifications could impose a huge influence on their performance. We report in this work how terminal amino acid modifications to G(IIKK)3I-NH2 influence its α-helical structure, membrane penetrating ability, and selective actions against different cell types. Deletion of an N-terminal Gly or a C-terminal Ile did not affect their antibacterial activity much, an observation consistent with their binding behavior to negatively charged membrane lipid monolayers. However, the cytotoxicity against mammalian cells was much worsened by the N-terminal Gly deletion, consistent with an increase in its helical content. Despite little impact on the antibacterial activity of G(IIKK)3I-NH2, deletion of both terminal amino acids greatly reduced its antitumor activity. Cholesterol present in tumor cell membrane-mimic was thought to constrain (IIKK)3-NH2 from penetrating into the cancerous membranes, evident from its lowest surface physical activity at penetrating model lipid membranes. On the other hand, its low toxicity to normal mammalian cells and high antibacterial activity in vitro and in vivo made it an attractive antibacterial agent. Thus, terminal modifications can help rebalance the different interactions involved and are highly effective at manipulating their selective membrane responses.Keywords: antibacterial peptide; cell selectivity; helical peptide; membrane penetration; surface pressure
Co-reporter:Yongfeng Yan, Yawei Sun, Haiyan Yu, Hai Xu and Jian R. Lu
Soft Matter 2015 vol. 11(Issue 9) pp:1748-1754
Publication Date(Web):02 Jan 2015
DOI:10.1039/C4SM02499K
This work describes the design and preparation of a simple but novel hybrid amphiphile containing a pH-responsive DNA sequence. The formation of a bimolecular i-motif structure allows the control of reversible switching of the hybrid amphiphile between the dimer and unimer by pH. Thus, spherical aggregates with distinct self-assembly pathways, sizes and structures are obtained at pH 4.5 and pH 9.0, and the structures can be switched by the change of pH and thermal annealing. This work reports different self-assembled nanostructures and their transitions that give this amphiphile potential for the design of controllable drug delivery systems.
Co-reporter:Shengjie Wang, Qingwei Cai, Mingxuan Du, Junyi Xue, and Hai Xu
The Journal of Physical Chemistry B 2015 Volume 119(Issue 36) pp:12059-12065
Publication Date(Web):August 24, 2015
DOI:10.1021/acs.jpcb.5b06455
Artificial synthesis of silica under benign conditions is usually achieved by using cationic organic matrices as templates while the anionic analogues have not received enough consideration, albeit they are also functioning in biosilica formation. In this work, we report the design and self-assembly of an anionic peptide amphiphile (I3E) and the use of its self-assemblies as templates to synthesize 1D silica nanostructures with tunable sizes. We show that short I3E readily formed long nanofibrils in aqueous solution via a hierarchical self-assembly process. By using APTES and TEOS as silica precursors, we found that the I3E nanofibrils templated the production of silica nanotubes with a wide size distribution, in which the silica size regulation was achieved by tuning the interactions among the peptide template and silicon species. These results clearly illustrate a facile method for generating silica nanomaterials based on anionic matrices.
Co-reporter:Chengdong Wang;Dr. Yawei Sun;Dr. Jiqian Wang; Hai Xu; Jian R. Lu
Chemistry – An Asian Journal 2015 Volume 10( Issue 9) pp:1953-1958
Publication Date(Web):
DOI:10.1002/asia.201500467
Abstract
The self-assembly of peptides and proteins under well-controlled conditions underlies important nanostructuring processes that could be harnessed in practical applications. Herein, the synthesis of a new hairpin peptide containing four histidine residues is reported and the self-assembly process mediated by metal ions is explored. The work involves the combined use of circular dichroism, NMR spectroscopy, UV/Vis spectroscopy, AFM, and TEM to follow the structural and morphological details of the metal-coordination-mediated folding and self-assembly of the peptide. The results indicate that by forming a tetragonal coordination geometry with four histidine residues, copper(II) ions selectively trigger the peptide to fold and then self-assemble into nanofibrils. Furthermore, the copper(II)-bound nanofibrils template the synthesis of CuS nanowires, which display a near-infrared laser-induced thermal effect.
Co-reporter:Yurong Zhao, Li Deng, Jiqian Wang, Hai Xu, and Jian R. Lu
Langmuir 2015 Volume 31(Issue 47) pp:12975-12983
Publication Date(Web):November 5, 2015
DOI:10.1021/acs.langmuir.5b02303
The structural modulation of peptide and protein assemblies under well-controlled conditions is of both fundamental and practical significance. In spite of extensive studies, it remains hugely challenging to tune the self-assembled nanostructures in a controllable manner because the self-assembly processes are dictated by various noncovalent interactions and their interplay. We report here how to manipulate the self-assembly of a designed, symmetric amphiphilic peptide (KI4K) via the solvent-controlled structural transition. Structural transition processes were carefully followed by the combination of transmission electronic microscopy (TEM), atomic force microscopy (AFM), circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), and small angle neutron scattering (SANS). The results show that the introduction of acetonitrile into water significantly affected the hydrophobic interactions among hydrophobic side chains while imposing little impact on the β-sheet hydrogen bonding between peptide backbones. A structural transition occurred from nanotubes to helical/twisted ribbons and then to thin fibrils with the addition of acetonitrile due to the reduced hydrophobic interactions and the consequent weakening of the lateral stacking between KI4K β-sheets. The increased intermolecular electrostatic repulsions among lysine side chain amino groups had little effect on the lateral stacking of KI4K β-sheets due to the molecular symmetry. Complementary molecular dynamic (MD) simulations also indicated the solvation of acetonitrile molecules into the hydrophobic domains weakening the coherence between the neighboring sheets.
Co-reporter:Meiwen Cao, Changhai Cao, Peng Zhou, Ningning Wang, Dong Wang, Jiqian Wang, Daohong Xia, Hai Xu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2015 Volume 469() pp:263-270
Publication Date(Web):20 March 2015
DOI:10.1016/j.colsurfa.2015.01.044
•Gemini peptides were produced by disulfide bond linkage of the single-chain ones.•The single-chain-to-gemini transition enhanced the self-assembly ability.•Gemini geometry introduced additional constraints in molecular conformation.•The intra- and intermolecular hydrogen bonding produced different structures.•Peptide self-assembly depended greatly on the side chain groups.By designing cysteine-containing single-chain peptides and then linking two such molecules with disulfide bond under oxidation, a series of amphiphilic gemini peptides were successfully synthesized. The gemini geometry introduced not only additional constraints in molecular conformations but also the differentiated intra- and intermolecular hydrogen bonding. These aspects result in specific transition of the self-assembly behavior. The single-chain peptides tended to form spherical aggregates, while the gemini molecules all self-assembled into fiber-like structures, especially that I3C–CI3 could form short thin fibers with highly ordered lateral alignments that are rarely found. Moreover, the self-assembly of both the single-chain and the gemini peptides showed great dependence on the side chain groups. With increasing the size of the side chain alkyl groups, the molecules gave decreased critical aggregation concentration (CAC) and were more ready to arrange into ordered assemblies. This should be ascribed to the enhanced hydrophobic interaction and the subsequent force balance shifts.The amphiphilic peptides self-assembled into different structures with variation of the side chain groups as well as the single-chain-to-gemini structural transition. The gemini geometry probably introduced additional constraints in molecular conformations and thus to result in specific molecular arrangements and self-assembled structures.
Co-reporter:Meiwen Cao, Li Deng, Hai Xu
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2015 470() pp: 46-51
Publication Date(Web):
DOI:10.1016/j.colsurfa.2015.01.063
Co-reporter:Cuixia Chen, Yanfeng Gu, Li Deng, Shuyi Han, Xing Sun, Yucan Chen, Jian R. Lu, and Hai Xu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 16) pp:14360
Publication Date(Web):August 4, 2014
DOI:10.1021/am5036303
Self-assembling peptide hydrogels with faster gelation kinetics and higher mechanical rigidity are favorable for their practical applications. A design strategy to control the folding, self-assembly, and hydrogelation of β-hairpin peptides via hydrophobic amino acid substitutions has been explored in this study. Isoleucine has higher hydrophobicity and stronger propensity for β-sheet hydrogen bonding than valine. After the valine residues of MAX1 (VKVKVKVKVDPPTKVKVKVKV-NH2) were replaced with isoleucines, oscillatory rheometry and circular dichroism (CD) spectroscopy characterizations indicated that the variants had clearly faster self-assembly and hydrogelation rates and that the resulting gels displayed higher mechanical stiffness. Transmission electron microscopy (TEM) indicated the parent MAX1 and its variants all formed networks of long and entangled fibrils with the similar diameters of ∼3 nm, suggesting little effect of hydrophobic substitutions on the self-assembled morphology. The MAX1I8 (IKIKIKIKVDPPTKIKIKIKI-NH2) hydrogel showed the fastest gelation rate (within 5 min) and the highest gel rigidity with the series, supporting the homogeneous cell distribution within its 3D scaffold. In addition, the MAX1I8 hydrogel showed quick shear-thinning and rapid recovery upon cessation of shear strain, and the MTT and immunological assays indicated its low cytotoxicity and good biocompatibility. These features are highly attractive for its widespread use in 3D cell culturing and regenerative medical treatments.Keywords: biomedical scaffold; gel rigidity; gelation kinetics; peptide hydrogel; residue substitution; β-hairpin peptide
Co-reporter:Cuixia Chen, Jing Hu, Ping Zeng, Yucan Chen, Hai Xu, and Jian R. Lu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 19) pp:16529
Publication Date(Web):September 11, 2014
DOI:10.1021/am504973d
On the basis of cell cultures involving bacterial strains (Escherichia coli 5α and Bacillus subtilis 168) and a mammalian cell line (NIH 3T3), the potent antibacterial activity and distinct selectivity from designed amphiphilic peptides G(IIKK)nI-NH2 (n = 2–4) have been demonstrated. This work extends these studies to multidrug resistant pathogens (ESBL-producing E. coli) and primary human cells (HDFa), followed by the in vivo mouse model investigation of ESBL-producing bacterial infection. G(IIKK)3I-NH2 exhibits high antibacterial activity against the pathogenic strain both in vitro and in vivo while displaying low toxicity toward the primary cells and the mice. Peptide molecules can kill bacteria by selectively interacting with bacterial membranes, causing structural disruptions. Furthermore, multidrug resistant ESBL-producing bacteria do not develop resistance after multiple treatments with G(IIKK)3I-NH2. The high cellular selectivity, low toxicity toward mammalian hosts and noninducing bacterial resistance indicate great potential for developing the peptides as anti-infection agents.Keywords: antimicrobial peptide; cell selectivity; drug resistance; ESBL-producing E. coli infection; helical peptide; membrane disruption
Co-reporter:Yawei Sun, Haiyan Yu, Yongfeng Yan, Cuixia Chen, Wenwen Xu, Jian R. Lu and Hai Xu
Soft Matter 2014 vol. 10(Issue 37) pp:7218-7224
Publication Date(Web):18 Jul 2014
DOI:10.1039/C4SM01374C
Two series of nucleolipids have been designed and synthesized, one with a varying chain length (the dT-Cn series) and the other incorporating an aromatic photo-responsive moiety at the molecular hydrophobic and hydrophilic interface (the P-dT-Cn series). Surface tension measurements revealed the variations of critical micelle concentrations (CMCs) with the alkyl chain length and the incorporation of the photo-responsive segment. The P-dT-Cn series showed broadly lower CMCs and the minimum area per molecule (Amin) values because the π–π stacking between the additional aromatic rings favours more tight packing in the micelle formation. Both series showed similar surface tensions at the CMCs to conventional surfactants with equivalent molecular structures. Their micellar aggregates were used for encapsulation of hydrophobic Nile Red (NR). For the P-dT-Cn series, the encapsulated NR was released upon light irradiation and the controlled release was readily realized by controlling irradiation intensities or switching on and off irradiation. The integration of biocompatibility, complementary base recognition and photo-responsiveness makes the amphiphilic nucleolipids promising in biomedical and biotechnological applications.
Co-reporter:Li Deng, Peng Zhou, Yurong Zhao, Yanting Wang, and Hai Xu
The Journal of Physical Chemistry B 2014 Volume 118(Issue 43) pp:12501-12510
Publication Date(Web):October 8, 2014
DOI:10.1021/jp506385j
In order to understand how microscopic molecular interactions between short peptides determine their mesoscopic self-assembled morphology, we studied the microscopic assembled structures of the short peptides I4K2 and KI4K, which have the same amino acid composition but different sequences, by using all-atom replica exchange molecular dynamics simulation. We found that, at room temperature, the difference in amino acid sequence does not apparently alter their strong propensity of forming β-sheets but does strongly affect their assembled stable structures and their appearance probabilities. These differences result from the competition between the electrostatic and hydrophobic interactions among the side chains of the molecules, which are linked up by hydrogen bonds formed between neighboring peptide backbones. Our simulation results not only reveal the molecular origin of the self-assembled morphological difference between I4K2 and KI4K but also demonstrate in general the subtle balance between electrostatic, hydrophobic, and hydrogen bonding interactions in short-peptide self-assembly.
Co-reporter:Yongqing Xia, Xinlong He, Meiwen Cao, Xiaojuan Wang, Yawei Sun, Hua He, Hai Xu, and Jian Ren Lu
Biomacromolecules 2014 Volume 15(Issue 11) pp:
Publication Date(Web):October 13, 2014
DOI:10.1021/bm501069w
Monodisperse poly(N-isopropylacrylamide-styrene) (PNIPAAmSt) microgels with different St/NIPAAm ratios have been synthesized via a one-step surfactant-free emulsion polymerization process. The resulting microgel dispersions were used to fabricate 2D arrays on the surface of silicon wafers/glass coverslips through dip coating. The thermal responsiveness of the PNIPAAmSt microgel arrays was examined by spectroscopic ellipsometry and the results unraveled that the thermoresponsive behavior of the arrays was highly consistent with the microgels dispersed in the bulk, showing high dependence on the content of styrene. The structure of the films varied from nonclose-packed 2D arrays to close-packed 2D arrays, depending on both properties of the microgels and array fabrication conditions. When the weight ratio of styrene was below 40%, the microgel arrays demonstrated effective control for cell growth and detachment across their volume phase transition temperatures (around 28 °C). The extent of swelling of the microgels was the key factor to determine whether the cells could detach from the film easily. For the rather close-packed 2D arrays prepared by the same kind of PNIPAAmSt microgels, the gaps between microgel particles showed no obvious effect on the rate of cell detachment.
Co-reporter:Cuixia Chen, Jing Hu, Ping Zeng, Fang Pan, Mohammed Yaseen, Hai Xu, Jian R. Lu
Biomaterials 2014 35(5) pp: 1552-1561
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.10.082
Co-reporter:JingHui Zhang;YuRong Zhao;ShuYi Han;CuiXia Chen
Science China Chemistry 2014 Volume 57( Issue 12) pp:1634-1645
Publication Date(Web):2014 December
DOI:10.1007/s11426-014-5234-4
Numerous peptides derived from naturally occurring proteins or de novo designed have been found to self-assemble into various nanostructures. These well-defined nanostructures have shown great potential for a variety of biomedical and biotechnological applications. In particular, surfactant-like peptides (SLPs) have distinctive advantages in their length, aggregating ability, and water solubility. In this article, we report recent advances in the mechanistic understanding of the self-assembly principles of SLPs and in their applications, most of which have been made in our laboratory. Hydrogen bonding between peptide backbones, hydrophobic interaction between hydrophobic side chains, and electrostatic repulsion between charged head groups all have roles in mediating the self-assembly of SLPs; the final self-assembled nanostructures are therefore dependent on their interplay. SLPs have shown diverse applications ranging from membrane protein stabilization and antimicrobial/anticancer agents to nanofabrication and biomineralization. Future advances in the self-assembly of SLPs will hinge on their large-scale production, the design of new functional SLPs with targeted properties, and the exploitation of new or improved applications.
Co-reporter:Hua He;Xing Sun;Xiaojuan Wang
Luminescence 2014 Volume 29( Issue 7) pp:837-845
Publication Date(Web):
DOI:10.1002/bio.2630
ABSTRACT
We compared the effects of several ligands frequently used in aqueous synthesis, including L-cysteine, L-cysteine hydrochloride, N-acetyl-L-cysteine (NAC), glutathione and 3-mercaptopropionic acid, for microwave synthesis of CdTe quantum dots (QDs) in a sealed vessel with varied temperatures and times, and then developed a rapid microwave-assisted protocol for preparing highly luminescent, photostable and biocompatible CdTe/CdS/ZnS core–multishell QDs. The effects of molecular structures of these ligands on QD synthesis under high temperatures were explored. Among these ligands, NAC was found to be the optimal ligand in terms of the optical properties of resultant QDs and reaction conditions. The emission wavelength of NAC-capped CdTe QDs could reach 700 nm in 5 min by controlling the reaction temperature, and the resultant CdTe/CdS/ZnS core–multishell QDs could achieve the highest quantum yields up to 74% with robust photostability. In addition, the effects of temperature, growth time and shell–precursor ratio on shell growth were examined. Finally, cell culturing indicated the low cytotoxicity of CdTe/CdS/ZnS core–multishell QDs as compared to CdTe and CdTe/CdS QDs, suggesting their high potential for applications in biomedical imaging and diagnostics. Copyright © 2014 John Wiley & Sons, Ltd.
Co-reporter:Yawei Sun, Yongfeng Yan, Mingqing Wang, Cuixia Chen, Hai Xu, and Jian R. Lu
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 13) pp:6232
Publication Date(Web):June 13, 2013
DOI:10.1021/am401169m
Amphiphilic hybrid nucleolipids bear the structural and functional hallmarks of both lipids and nucleic acids and hold great potential for biotechnological applications. However, further tailoring of their structures and properties for specific applications represents a major challenge. We here report a novel design and synthesis of a light-responsive nucleolipid by introducing an o-nitrobenzyl group that acts as a linker between a nucleotide and a lipid. The nucleolipid was applied readily to preparing smart vesicles and encapsulating hydrophilic guest molecules 5(6)-carboxyfluorescein (CF) in their inner aqueous phase. Upon light irradiation, their vesicular structure was disrupted as a result of the photolytic degradation of the nucleotide, resulting in CF release. Furthermore, temporally controlled CF release from these vesicles could be readily realized by turning on and off light. By demonstrating the molecular assembly and photodisassembly cycle, this report aims to stimulate further research exploring practical applications of nucleolipids.Keywords: controlled release; nucleolipid; photolabile; vesicle;
Co-reporter:Kang Zhao, Meng Wang, Xiaoqiang Wang, Congmeng Wu, Hai Xu, and Jian R. Lu
Crystal Growth & Design 2013 Volume 13(Issue 4) pp:1583-1589
Publication Date(Web):March 12, 2013
DOI:10.1021/cg301820w
Ovalbumin and lysozyme are two major egg white proteins and putatively related to the formation of the mammillary layer of eggshells. In this work, we have investigated their influences on the morphology and growth kinetics of hillocks at the molecular scale using fluid-cell atomic force microscopy. Our studies identified two roles for ovalbumin, favoring the formation of amorphous calcium carbonate–protein clusters on terrace surface and accelerating the step growth kinetics via reduction of the energy barrier for ion attachment to crystal steps. The two effects are intimately linked to the inherent characteristics of ovalbumin, i.e., being acidic and amphiphilic. In contrast, lysozyme as a basic protein did not induce the formation of any moldable transient phases. Instead, it interacted with step edges and pinned them, leading to step bunching and even step advancement stop at higher concentrations. These roles and their associated interactions on the molecular scale are related to the macroscopic features of eggshells and provide a reliable basis for further investigation into their influences in more complex systems mimicking native biological environment.
Co-reporter:Hai Xu, Cui Xia Chen, Jing Hu, Peng Zhou, Ping Zeng, Chang Hai Cao, Jian Ren Lu
Biomaterials 2013 34(11) pp: 2731-2737
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.12.039
Co-reporter:Yurong Zhao, Jiqian Wang, Li Deng, Peng Zhou, Shengjie Wang, Yanting Wang, Hai Xu, and Jian R. Lu
Langmuir 2013 Volume 29(Issue 44) pp:13457-13464
Publication Date(Web):October 3, 2013
DOI:10.1021/la402441w
Peptide self-assembly is of direct relevance to protein science and bionanotechnology, but the underlying mechanism is still poorly understood. Here, we demonstrate the distinct roles of the noncovalent interactions and their impact on nanostructural templating using carefully designed hexapeptides, I2K2I2, I4K2, and KI4K. These simple variations in sequence led to drastic changes in final self-assembled structures. β-sheet hydrogen bonding was found to favor the formation of one-dimensional nanostructures, such as nanofibrils from I4K2 and nanotubes from KI4K, but the lack of evident β-sheet hydrogen bonding in the case of I2K2I2 led to no nanostructure formed. The lateral stacking and twisting of the β-sheets were well-linked to the hydrophobic and electrostatic interactions between amino acid side chains and their interplay. For I4K2, the electrostatic repulsion acted to reduce the hydrophobic attraction between β-sheets, leading to their limited lateral stacking and more twisting, and final fibrillar structures; in contrast, the repulsive force had little influence in the case of KI4K, resulting in wide ribbons that eventually developed into nanotubes. The fibrillar and tubular features were demonstrated by a combination of cryogenic transmission electron microscopy (cryo-TEM), negative-stain transmission electron microscopy (TEM), and small-angle neutron scattering (SANS). SANS also provided structural information at shorter scale lengths. All atom molecular dynamics (MD) simulations were used to suggest possible molecular arrangements within the β-sheets at the very early stage of self-assembly.
Co-reporter:Yongqing Xia, Xinlong He, Meiwen Cao, Cuixia Chen, Hai Xu, Fang Pan, and Jian Ren Lu
Biomacromolecules 2013 Volume 14(Issue 10) pp:
Publication Date(Web):August 26, 2013
DOI:10.1021/bm4009765
This work reports the formation of thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAmSt) microgel films and their use for cell growth and detachment via temperature stimuli. Thermoresponsive surface films can be conveniently produced by spin-coating or drop-coating of PNIPAAmSt microgel dispersions onto substrates such as glass coverslips, cell culture plates, and flasks, making this technique widely accessible. The thickness, stability, and reversibility of the PNIPAAmSt films coated on silicon wafers with respect to temperature switching were examined by spectroscopic ellipsometry (SE) and atomic force microscopy (AFM). The results unraveled the direct link between thermoreversibility and changes in film thickness and surface morphology, showing reversible hydration and dehydration. Under different coating conditions, well-packed microgel monolayers could be utilized for effective cell recovery and harvesting. Furthermore, cell adhesion and detachment processes were reversible and there was no sign of loss of cell viability during repeated surface attachment, growth, and detachment, showing a mild interaction between cells and thermoresponsive surface. More importantly, there was little deterioration of the packing of the thermoresponsive films or any major loss of microgel particles during reuse, indicating their robustness. These PNIPAAmSt microgel films thus open up a convenient interfacial platform for cell and cell sheet harvesting while avoiding the damage of enzymatic cleavage.
Co-reporter:Hua He, Min Feng, Jing Hu, Cuixia Chen, Jiqian Wang, Xiaojuan Wang, Hai Xu, and Jian R. Lu
ACS Applied Materials & Interfaces 2012 Volume 4(Issue 11) pp:6362
Publication Date(Web):October 29, 2012
DOI:10.1021/am3020108
We have designed a series of short RGD peptide ligands and developed one-pot aqueous synthesis of integrin-binding CdTe and CdZnTe quantum dots (QDs). We first examined the effects of different RGD peptides, including RGDS, CRGDS, Ac-CRGDS, CRGDS-CONH2, Ac-CRGDS-CONH2, RGDSC, CCRGDS, and CCCRGDS, on the synthesis of CdTe QDs. CRGDS were found to be the optimal ligand, providing the CdTe QDs with well-defined wavelength ranges (500–650 nm) and relatively high photoluminescence quantum yields (up to 15%). The key synthesis parameters (the pH value of the Cd2+-RGD precursors and the molar ratio of RGD/Cd2+) were assessed. In order to further improve the optical properties of the RGD-capped QDs, zinc was then incorporated by the simultaneous reaction of Cd2+ and Zn2+ with NaHTe. By using a mixture of CRGDS and cysteine as the stabilizer, the quantum yields of CdZnTe alloy QDs reached as high as 60% without any post-treatment, and they also showed excellent stability against time, pH, and salinity. Note that these properties could not be obtained with CRGDS or cysteine alone as the stabilizer. Finally, we demonstrated that the RGD-capped QDs preferentially bind to cell surfaces because of the specific recognition of the RGD sequence to cell surface integrin receptors. Our synthesis strategy based on RGD peptides thus represents a convenient route for opening up QD technologies for cell-specific tagging and labeling applicable to a wide range of diagnostics and therapy.Keywords: biorecognition; CdTe; CdZnTe; quantum dots; RGD peptides;
Co-reporter:Shengjie Wang, Junyi Xue, Xin Ge, Haiming Fan, Hai Xu and Jian R. Lu
Chemical Communications 2012 vol. 48(Issue 75) pp:9415-9417
Publication Date(Web):31 Jul 2012
DOI:10.1039/C2CC34667B
By manipulating the interfacial interactions between the peptide templates and the silicate species derived from TEOS and APTES, a facile biomimetic method was developed for the fabrication of silica nanostructures exhibiting “string-of-beads” and fibrillar morphologies of varied sizes.
Co-reporter:Congmeng Wu, Kang Zhao, Xiaoqiang Wang, Meiwen Cao, Hai Xu, and Jian R. Lu
Crystal Growth & Design 2012 Volume 12(Issue 5) pp:2594-2601
Publication Date(Web):April 6, 2012
DOI:10.1021/cg300194v
In the presence of aspartic acid (Asp), the calcite (104) face shows distinct dissolution pit morphology, presumably resulting from the surface reaction between calcite and Asp. However, the specific nature of this interaction and the influence of solution hydrodynamics remain unclear. To this end, we have followed the calcite (104) surface dissolution using in situ fluid cell atomic force microscopy (AFM). The results showed that at pH 4.5 and in 100 mM Asp the surface reactions were controlled by diffusion under static conditions and that trapezoidal etch pits were formed. In contrast, elliptical etch pits were rapidly developed upon flowing due to the increased transfer of Asp to the [010] step edge and the dissolution of Asp-surface complexes away from the step edge. The occurrence of the [010], [461̅], and [4̅11] steps of trapezoidal etch pits was attributed to the stabilization of the (001), (1̅12), and (01̅1) faces by Asp through bridging between the two carboxyl groups and two adjacent Ca atoms, with the α-NH3+ group forming a hydrogen bond with the oxygen of the H2O from the bulk solution and the surface CO3 groups from the (1̅12) and (01̅1) faces. The mirror images of the etch pits formed in d-Asp and l-Asp solutions resulted from the enantio-specific interaction, supporting the tripodal contact of Asp with the crystal surface. Thus, the etch pit morphology is affected by Asp concentration, mass transfer, and specific surface reaction.
Co-reporter:Daoyong Yu, Fang Huang and Hai Xu
Analytical Methods 2012 vol. 4(Issue 1) pp:47-49
Publication Date(Web):18 Nov 2011
DOI:10.1039/C1AY05495C
We demonstrate that by using constant wavelength synchronous fluorescence spectrometry (CW-SFS) critical concentrations of some types of aggregation can be quantified. Detection of aggregation associated with hydrogen bonding in Chlorin e6 and Triton X-100 suggest that CW-SFS may be a technique that can explore aggregation at much lower levels (dimer, trimer, oligomer, etc.)
Co-reporter:ChangHai Cao;MeiWen Cao;HaiMing Fan;DaoHong Xia
Science Bulletin 2012 Volume 57( Issue 33) pp:4296-4303
Publication Date(Web):2012 November
DOI:10.1007/s11434-012-5487-2
Hydrogels resulting from the self-assembly of small peptides are smart nanobiomaterials as their nanostructuring can be readily tuned by environmental stimuli such as pH, ionic strength and temperature, thereby favoring their practical applications. This work reports experimental observations of formation of peptide hydrogels in response to the redox environment. Ac-I3K-NH2 is a short peptide amphiphile that readily self-assembles into long nanofibers and its gel formation occurs at concentrations of about 10 mmol/L. Introduction of a Cys residue into the hydrophilic region leads to a new molecule, Ac-I3CGK-NH2, that enables the formation of disulfide bonds between self-assembled nanofibers, thus favoring cross-linking and promoting hydrogel formation. Under oxidative environment, Ac-I3CGK-NH2 formed hydrogels at much lower concentrations (even at 0.5 mmol/L). Furthermore, the strength of the hydrogels could be easily tuned by switching between oxidative and reductive conditions and time. However, AFM, TEM, and CD measurements revealed little morphological and structural changes at molecular and nano dimensions, showing no apparent influence arising from the disulfide bond formation.
Co-reporter:Yongqing Xia, Yanfeng Gu, Xuan Zhou, Hai Xu, Xiubo Zhao, Mohammed Yaseen, and Jian Ren Lu
Biomacromolecules 2012 Volume 13(Issue 8) pp:
Publication Date(Web):June 20, 2012
DOI:10.1021/bm300539f
Two types of thermoresponsive microgels, poly(N-isopropylacrylamide) (PNIPAM) microgels and poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAMAC) microgels were synthesized and used as templates for the mineralization of amorphous calcium carbonate (ACC) by diffusion of CO2 vapor under ambient conditions. Thermosensitive PNIPAM/CaCO3 hybrid macroscopic hydrogels and micrometer-sized PNIPAMAC/CaCO3 hybrid microgels were controllably obtained and different mineralization mechanistic processes were proposed. The impact of the loaded CaCO3 on the size, morphology, stability, and thermosensitivity of the microgels was also analyzed. PNIPAM/CaCO3 hybrid macrogels had a slight decrease in thermoresponsive phase transition temperature, while PNIPAMAC/CaCO3 hybrid microgels showed a clear increase in phase transition temperature. The difference reflected different amount and location of ACC in the gel network, causing different interactions with polymer chains. The PNIPAMAC/CaCO3 microgels formed stable monolayer films on bare silica wafers and glass coverslips upon drying. The microgel films could facilitate the attachment and growth of 3T3 fibroblast cells and their subsequent detachment upon temperature drop from 37 °C to the ambient condition around 20 °C, thus, offering a convenient procedure for cell harvesting.
Co-reporter:Cuixia Chen, Jing Hu, Shengzhong Zhang, Peng Zhou, Xichen Zhao, Hai Xu, Xiubo Zhao, Mohammed Yaseen, Jian R. Lu
Biomaterials 2012 33(2) pp: 592-603
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.09.059
Co-reporter:Shengjie Wang, Xin Ge, Junyi Xue, Haiming Fan, Linjia Mu, Yanpeng Li, Hai Xu, and Jian R. Lu
Chemistry of Materials 2011 Volume 23(Issue 9) pp:2466
Publication Date(Web):April 14, 2011
DOI:10.1021/cm2003885
This work reports a mechanistic study of template-directed synthesis of silica nanomaterials utilizing self-assembled peptide nanotubes as scaffolds. An ultrashort amphiphilic peptide (I3K) underwent self-assembly in aqueous solution under ambient conditions to form long and uniform nanotubes. The assembled peptide nanotubes then were used as templates for the subsequent fabrication of silica nanotubes from tetraethoxysilane (TEOS), also under ambient conditions. In order to gain better insight into the mediation of peptide self-assembly on the formation of silica nanostructures, we have carefully investigated environmental influences including the concentrations of peptide and silica precursor, solution pH, and reaction time, with the full screening of the processes by TEM, SEM, 29Si MAS NMR, FTIR, and TG-MS. The results revealed that, while peptide nanotubes worked as scaffolds for the formation of tubular silica structures, the surfaces of these peptide nanotubes served as catalytic sites for both hydrolysis and condensation of TEOS, thereby working as templates for directing silica deposition. Because the electrostatic attraction of the negatively charged silica intermediates onto the positively charged surface of peptide nanotubes drove the templating process, tuning of such an interaction by adjusting the solution conditions (such as pH) affected silica morphological structures. Silica tended to deposit along the exterior surface of the template at undersaturation over weak acidic and neutral pH ranges, while silica intermediates overcame diffusion resistance and moved inside the tubular template over mild basic pH ranges, enabling silica precipitation along the interior surface. This work has thus demonstrated that the morphological nanostructures of silica can be controlled by adjusting the silicification conditions (such as peptide concentration and solution pH) under an ambient environment, thus avoiding harsh chemicals or extreme reaction conditions.Keywords: biomimetic silicification; biomimetic synthesis; I3K; peptide amphiphiles; peptide nanotubes; peptide templates; silica nanostructures; silica nanotubes;
Co-reporter:Congmeng Wu, Xiaoqiang Wang, Kang Zhao, Meiwen Cao, Hai Xu, Daohong Xia, and Jian R. Lu
Crystal Growth & Design 2011 Volume 11(Issue 7) pp:3153
Publication Date(Web):May 18, 2011
DOI:10.1021/cg200403t
Dissolution of the calcite (104) surface in aqueous solution in the presence of 10 organic acids has been studied using fluid-cell atomic force microscopy (AFM) in vitro. Etch pit morphology varies as species conformation changes. [421̅] steps appeared in the presence of each of Gly, l-Glu, l-Lys, malonate, and succinate. The overall shape of etch pits became hexagonal in Gly, malonate, and succinate, while a pseudotriangular shape in l-Glu solution and a sectorial shape in l-Lys solution were observed, primarily as a result of molecular chirality. Unexpectedly, [010] instead of [421̅] steps emerged in l-Asp solution, giving a trapezoidal pit shape. Despite the differences in molecular structure of 6-aminohexanoate, acetate, oxalate, and glutarate, these molecules did not show any influence on pit morphology, revealing that solid/fluid recognition must depend on the geometry of additives, especially the distance between functional groups. We show that both the ammonium and the carboxylate groups are active in surface binding and that the organic acids tend to bind through more than one functional group to the calcite face. Our AFM results confirm the crucial role of geometrical matching between calcite and modifiers and show that step edge reactivity, stereochemical correspondence, electrostatic attraction, and molecular chirality play a secondary role in surface modification. This conclusion will give guidelines for synthesizing bioinspired materials with specific shape.
Co-reporter:Jing Hu, Cuixia Chen, Shengzhong Zhang, Xichen Zhao, Hai Xu, Xiubo Zhao, and Jian R. Lu
Biomacromolecules 2011 Volume 12(Issue 11) pp:
Publication Date(Web):September 28, 2011
DOI:10.1021/bm201098j
We report a new class of cationic amphiphilic peptides with short sequences, G(IIKK)nI-NH2 (n = 1–4), that can kill Gram-positive and Gram-negative bacteria as effectively as several well-known antimicrobial peptides and antibiotics. In addition, some of these peptides possess potent antitumor activities against cancer cell lines. Moreover, their hemolytic activities against human red blood cells (hRBCs) remain remarkably low even at some 10-fold bactericidal minimum inhibitory concentrations (MICs). When bacteria or tumor cells are cocultured with NIH 3T3 fibroblast cells, G(IIKK)3I-NH2 showed fast and strong selectivity against microbial or tumor cells, without any adverse effect on NIH 3T3 cells. The high selectivity and associated features are attributed to two design tactics: the use of Ile residues rather than Leu and the perturbation of the hydrophobic face of the helical structure with the insertion of a positively charged Lys residue. This class of simple peptides hence offers new opportunities in the development of cost-effective and highly selective antimicrobial and antitumor peptide-based treatments.
Co-reporter:Meiwen Cao, Yuming Wang, Xin Ge, Changhai Cao, Jing Wang, Hai Xu, Daohong Xia, Xiubo Zhao, and Jian R. Lu
The Journal of Physical Chemistry B 2011 Volume 115(Issue 41) pp:11862-11871
Publication Date(Web):September 6, 2011
DOI:10.1021/jp205987w
The effects of addition of a series of stoichiometric salts on the nanostructuring of cationic amphiphilic peptides have been investigated through the combination of atomic force microscopy (AFM), circular dichroism (CD), and turbidity measurements. The results revealed that anions had more pronounced effects than cations in tuning the nanostructures formed from these peptides. Addition of ClO3–, NO3–, and Br– could stabilize the primary nanostructures (nanostacks, nanospheres, or short nanorods) formed by A9K and I3K and effectively inhibit their growth into longer nanostructures (nanorods or nanotubes). In contrast, the anions of Cl–, SO42–, HPO42–, PO43–, and C6H5O73– (citrate) favored the axial growth of these peptides to form long intersecting nanofibrils and led to an increase in diameter and surface roughness, as well, clearly enhancing their propensity for nanostructuring. The efficiency of different anions in promoting the growth of peptide nanoaggregates into larger ones could be ordered as ClO3– < NO3– ≤ Br– < Cl– < SO42– < HPO42– < PO43– < C6H5O73–, broadly consistent with the Hofmeister anion sequence. These observations were well rationalized by considering different aspects of direct interactions of the anions with the peptide molecules.
Co-reporter:Shuyi Han;Sasa Cao;Yuming Wang;Dr. Jiqian Wang; Daohong Xia; Hai Xu;Dr. Xiubo Zhao; Jian R. Lu
Chemistry - A European Journal 2011 Volume 17( Issue 46) pp:13095-13102
Publication Date(Web):
DOI:10.1002/chem.201101970
Abstract
The interplay between hydrogen bonding, hydrophobic interaction and the molecular geometry of amino acid side-chains is crucial to the development of nanostructures of short peptide amphiphiles. An important step towards developing their practical use is to understand how different amino acid side-chains tune hydrophobic interaction and hydrogen bonding and how this process leads to the control of the size and shape of the nanostructures. In this study, we have designed and synthesized three sets of short amphiphilic peptides (I3K, LI2K and L3K; L3K, L4K and L5K; I3K, I4K and I5K) and investigated how I and L affected their self-assembly in aqueous solution. The results have demonstrated a strong tendency of I groups to promote the growth of β-sheet hydrogen bonding and the subsequent formation of nanofibrillar shapes. All ImK (m=3–5) peptides assembled into nanofibers with consistent β-sheet conformation, whereas the nanofiber diameters decreased as m increased due to geometrical constraint in peptide chain packing. In contrast, L groups had a weak tendency to promote β-sheet structuring and their hydrophobicity became dominant and resulted in globular micelles in L3K assembly. However, increase in the number of hydrophobic sequences to L5K induced β-sheet conformation due to the cooperative hydrophobic effect and the consequent formation of long nanofibers. The assembly of L4K was, therefore, intermediate between L3K and L5K, similar to the case of LI2K within the set of L3K, LI2K and I3K, with a steady transition from the dominance of hydrophobic interaction to hydrogen bonding. Thus, changes in hydrophobic length and swapping of L and I can alter the size and shape of the self-assembled nanostructures from these simple peptide amphiphiles.
Co-reporter:Kai Tao, Jiqian Wang, Peng Zhou, Chengdong Wang, Hai Xu, Xiubo Zhao, and Jian R. Lu
Langmuir 2011 Volume 27(Issue 6) pp:2723-2730
Publication Date(Web):February 10, 2011
DOI:10.1021/la1034273
We report the characterization of self-assembly of two short β-amyloid (Aβ) peptides (16−22), KLVFFAE and Ac-KLVFFAE-NH2, focusing on examining the effect of terminal capping. At pH 2.0, TEM and AFM imaging revealed that the uncapped peptide self-assembled into long, straight, and unbranched nanofibrils with a diameter of 3.8 ± 1.0 nm while the capped one formed nanotapes with a width of 70.0 ± 25.0 nm. CD analysis indicated the formation of β-sheet structures in both aggregated systems, but the characteristic CD peaks were less intense and less red-shifted for the uncapped than the capped one, indicative of weaker hydrogen bonding and weaker π−π stacking. Fluorescence and rheological measurements also confirmed stronger intermolecular attraction associated with the capped nanotapes. At acidic pH 2, each uncapped KLVFFAE molecule carries two positive charges at the N-terminus, and the strong electrostatic repulsion favors interfacial curving and twisting within the β-sheet, causing weakening of hydrogen bonds and π−π stacking. In contrast, capping reduces the charge by half, and intermolecular electrostatic repulsion is drastically reduced. As a result, the lateral attraction of β-sheets favors stronger lamellar structuring, leading to the formation of rather flat nanotapes. Flat tapes with similar morphological structure were also formed by the capped peptide at pH 12.0 where the charge on the capping end was reversed. This study has thus demonstrated how self-assembled nanostructures of small peptides can be manipulated through simple molecular structure design and tuning of electrostatic interaction.
Co-reporter:Hai Xu, Yuming Wang, Xin Ge, Shuyi Han, Shengjie Wang, Peng Zhou, Honghong Shan, Xiubo Zhao, and Jian R. Lu
Chemistry of Materials 2010 Volume 22(Issue 18) pp:5165
Publication Date(Web):August 17, 2010
DOI:10.1021/cm101019p
Many de novo designed amphiphilic peptides capable of self-assembly and further structural templating into hierarchical organizations such as nanofibers and gels carry more than 10 amino acid residues. A curious question is now raised about the minimal size that is required for initiating amphiphilically driven nanostructuring. In this work, we show that ultrashort peptides I3K and L3K could readily self-assemble into stable nanostructures. While L3K formed spherical nanospheres with diameters of ∼10−15 nm, I3K self-assembled into nanotubes with diameters of ∼10 nm and lengths of >5 μm. I3K nanotubes were very smooth and carried defined pitches of twisting. The difference could arise from the different β-sheet promoting power between isoleucine and leucine, suggesting that while hydrophobic interaction was dominant in the formation of L3K nanospheres hydrogen bonding governed the templating of antiparallel β-sheets and the subsequent formation of I3K nanotubes. Because of their extreme stability against heating or exposure to organic solvents, I3K nanotubes were used as templates for silicification from the hydrolysis of organosilicate precursors using TEOS (tetraethoxysilane). The lysine groups on the inner and outer nanotube surfaces worked to catalyze silicification, leading to the formation of silica nanotubes, which is evident from both AFM and TEM imaging. The formation of interesting nanotubes and nanospheres as demonstrated from very short peptide amphiphiles is significant for further exploration of their use in technological applications.
Co-reporter:Cuixia Chen, Fang Pan, Shengzhong Zhang, Jing Hu, Meiwen Cao, Jing Wang, Hai Xu, Xiubo Zhao and Jian R. Lu
Biomacromolecules 2010 Volume 11(Issue 2) pp:
Publication Date(Web):January 15, 2010
DOI:10.1021/bm901130u
Amphiphilic peptides A3K, A6K, and A9K displayed an increasing propensity for nanoaggregation with increasing the size of hydrophobic alanine moiety, and the size and shape of the aggregates showed a steady transition from loose peptide stacks formed by A3K, long nanofibers by A6K, to short and narrow nanorods by A9K. This size and shape transition was broadly consistent with the trend predicted from interfacial packing and curvature change if these peptide surfactants were treated as conventional surfactants. The antibacterial capacity, defined by the killing of percentage of bacteria in a given time and peptide concentration, showed a strong correlation to peptide hydrophobicity, evident from both microscopic and fluorescence imaging studies. For A9K, the power for membrane permeation and bacterial clustering intensified with peptide concentration and incubation time. These results thus depict a positive correlation between the propensity for self-assembly of the peptides, their membrane penetration power, and bactericidal capacity. Although the exposure of A9K to a preformed DPPC membrane bilayer showed little structural disturbance, the same treatment to the preformed DPPG membrane bilayer led to substantial disruption of model membrane structure, a trend entirely consistent with the high selectivity observed from membrane hemolytic studies.
Co-reporter:Xiaoqiang Wang, Congmeng Wu, Kai Tao, Kang Zhao, Jiqian Wang, Hai Xu, Daohong Xia, Honghong Shan and Jian R. Lu
The Journal of Physical Chemistry B 2010 Volume 114(Issue 16) pp:5301-5308
Publication Date(Web):April 6, 2010
DOI:10.1021/jp1008237
As a major constituent of egg white matrix, ovalbumin has long been perceived to be implicated in the formation of avian eggshells, in particular, the mammillary layer. However, very little is known about the detailed mechanism by which this protein mediates shell calcification. By the combined studies of AFM, SEM, and TEM, we have investigated the influence of ovalbumin on CaCO3 precipitation under in vitro mineralization conditions. We observed that the influence was multifold. This protein modified the morphology of calcite crystals through a distinct anisotropic process with respect to the four crystal step edges. AFM characterization revealed that the modification was initiated at the obtuse−obtuse step corner and propagated predominantly along the obtuse steps. Furthermore, the protein favored the existence of unstable phases such as amorphous calcium carbonate and crystalline vaterite. In contrast, lysozyme, another protein also present in the system, played a very different role in modifying calcite morphology. The mechanistic understanding gained from this study is clearly also of practical significance in developing advanced inorganic CaCO3 materials with the aid of morphological manipulation of crystalline structures via different protein mediation.
Co-reporter:Xiaoqiang Wang, Hailing Sun, Yongqing Xia, Cuixia Chen, Hai Xu, Honghong Shan, Jian R. Lu
Journal of Colloid and Interface Science 2009 Volume 332(Issue 1) pp:96-103
Publication Date(Web):1 April 2009
DOI:10.1016/j.jcis.2008.12.055
Lysozyme, a major component of egg white proteins, has been speculated to participate in the calcification of avian eggshells. However, its detailed role during the eggshell formation is not well understood. In this work, the influence of lysozyme on the precipitation of CaCO3 has been investigated using a combined study of FTIR, XRD, and SEM. The precipitation was produced from (NH4)2CO3 vapor diffusion into CaCl2 aqueous solution using a specially built chamber. In the absence of lysozyme, hexagonal platelets of vaterite and their spherical aggregates dominated the precipitates during the first 3–12 h crystallization period studied, with the (001) crystal face well expressed in the hexagonal direction. In contrast, calcite was favored to precipitate in the presence of lysozyme during the same period and the effect was found to be proportional to lysozyme concentration. Furthermore, the (110) face of calcite was expressed in addition to the common (104) face, and the morphological modification was also lysozyme concentration dependent. We attributed these phenomena to the selective adsorption of ammonium ions and lysozyme onto different crystal faces. Our findings have clearly revealed the concentration and face dependent role of lysozyme in CaCO3 precipitation. This, together with the abundance of lysozyme in the uterine fluid, implies its direct contribution to the hierarchical structures of calcite during the initial stage of eggshell formation.The presence of lysozyme favored the precipitation of calcite crystals and the influence is protein concentration dependent.
Co-reporter:Xiaoqiang Wang, Rui Kong, Xiaoxiao Pan, Hai Xu, Daohong Xia, Honghong Shan and Jian R. Lu
The Journal of Physical Chemistry B 2009 Volume 113(Issue 26) pp:8975-8982
Publication Date(Web):June 4, 2009
DOI:10.1021/jp810281f
The role of proteins in biomineralization has been examined in this work by studying the effect of ovalbumin on the stabilization of metastable CaCO3 phases. In the absence of ovalbumin, the mixing of Na2CO3 with CaCl2 in an aqueous solution led to the formation of metastable phases that swiftly transformed into stable calcite crystals within 4 h under the experimental conditions. However, ovalbumin was found to favor the formation and stabilization of spherical vaterites, and the effect was concentration dependent. In the presence of 2 g/L ovalbumin, for example, vaterite microspheres with diameters ranging from 0.9 to 3.0 μm, composed of much smaller nanosized particles, were produced and stabilized even after 24 h following the initial mixing. In addition, the influence of ovalbumin on the CaCO3 mineralization process from the very beginning was carefully examined. Both amorphous calcium carbonate (ACC) and vaterite were favored with ovalbumin present, but the ACC phase formed predominantly at the initial stage of mixing followed by the vaterite formation. Vaterite could then be embedded further in the mineralization process and become stabilized many hours afterward. The stabilizing effect of ovalbumin could arise from the strong binding between carboxylate groups of ovalbumin and the calcium ions on the CaCO3 surface, preventing the metastable CaCO3 from transformation via dissolution−recrystallization processes. The strong ovalbumin adsorption on vaterite microspheres was revealed from transmission electron microscopy imaging and thermogravimetric analysis, thereby providing useful evidence to support the proposed stabilizing mechanism.
Co-reporter:Hai Xu, Jing Wang, Shuyi Han, Jiqian Wang, Daoyong Yu, Hongyu Zhang, Daohong Xia, Xiubo Zhao, Thomas A. Waigh and Jian R. Lu
Langmuir 2009 Volume 25(Issue 7) pp:4115-4123
Publication Date(Web):December 29, 2008
DOI:10.1021/la802499n
Peptide amphiphiles readily self-assemble into a variety of nanostructures, but how molecular architectures affect the size and shape of the nanoaggregates formed is not well understood. From a combined TEM and AFM study of a series of cationic peptide surfactants AmK (m = 3, 6, and 9), we show that structural transitions (sheets, fibers/worm-like micelles, and short rods) can be induced by increasing the length of the hydrophobic peptide region. The trend can be interpreted using the molecular packing theory developed to describe surfactant structural transitions, but the entropic gain, decreased CAC, and increased electrostatic interaction associated with increasing the peptide hydrophobic chain need to be taken into account appropriately. Our analysis indicates that the trend in structural transitions observed from AmK peptide surfactants is opposite to that obtained from conventional monovalent ionic surfactants. The outcome reflects the dominant role of hydrophobic interaction between the side chains opposed by backbone hydrogen bonding and electrostatic repulsion between lysine side chains.
Co-reporter:Xiaoqiang Wang, Yuming Wang, Hai Xu, Honghong Shan, Jian R. Lu
Journal of Colloid and Interface Science 2008 Volume 323(Issue 1) pp:18-25
Publication Date(Web):1 July 2008
DOI:10.1016/j.jcis.2008.04.024
Spectroscopic ellipsometry (SE) and atomic force microscopy (AFM) have been used to investigate the adsorption of a mouse monoclonal antibody (type IgG1, anti-β-hCG) on hydrophilic silica (bearing weak negative charges above pH 3), followed by the assessment of binding of human chorionic gonadotrophin (hCG). The antibody is a relatively large molecule with a molecular weight of 150 kDa and the isoelectric point (IP) around pH 6. The antibody adsorption was conducted at pH 4.0, 6.0 and 8.0 to examine the role of charge interaction. Ellipsometric results show that away from the IP, both initial adsorption rate and surface excess decreased, with the reduction at pH 8.0 being more pronounced than that at pH 4.0 due to the electrostatic repulsion not only between the charged antibody molecules within the adsorbed layer but also between antibody and the silica surface. Whilst parallel AFM measurements confirmed the main trend of pH dependent antibody adsorption, they also revealed the tendency of surface aggregation with increasing surface coverage. AFM height profiling at low surface coverage confirmed the “flat-on” orientation of adsorbed antibody molecules, consistent with the previous study by neutron reflection. Interestingly, the antibody height at pH 4.0 was found to be lower than that at pH 8.0, showing the influence from different electrostatic interactions under the two pH conditions. Subsequent hCG binding to the adsorbed antibodies was found to decrease with increasing surface coverage due to the steric hindrance. Under similar antibody surface coverage, the hCG binding ratio at pH 8 was higher than that at pH 4.0, a difference that could only be accounted for by the tighter surface confinement at pH 4.0.Specific binding of antigen hCG to pre-adsorbed antibody anti-hCG (▵) compared to the control (○).
Co-reporter:Cuixia Chen, Jing Hu, Cheng Yang, Yu Zhang, Fang Wang, Quanmeng Mu, Fang Pan, Hai Xu and Jian Ren Lu
Journal of Materials Chemistry A 2016 - vol. 4(Issue 13) pp:NaN2368-2368
Publication Date(Web):2016/03/03
DOI:10.1039/C6TB00155F
The artificially designed amphiphilic peptide G(IIKK)3I-NH2 has been shown to be highly effective at killing bacteria and inhibiting the growth of tumor cells whilst remaining benign to normal mammalian cells. Herein we report how the side chain length and branching of constituent amino acids affect these bioactivities. Two peptide groups were designed by utilizing G(IIKK)3I-NH2 as the base template. In Group 1, hydrophobic residues were replaced from Ile to Leu, Nle (norleucine), or Val. It was found that an increase in the side chain carbon number from 3 (Val) to 4 (Leu, Ile or Nle) substantially enhanced their antibacterial and antitumor activities, but different branching in the butyl side chain showed very different cytotoxicities to host mammalian cells, with the γ-branching in Leu eliciting the highest potency. Group 2 covered those cationic Lys residues which were replaced by synthetic homologues with shorter side chains, namely, Orn, Dab and Dap containing 3, 2 and 1 methylene units, respectively. The replacement did not affect their antibacterial activities much, but their anticancer activities were maximized in Orn and Dab. On the other hand, their cytotoxicities also became higher, indicating a multi-faceted role played by the cationic residues. Thus, changes in both the side chain length and branching strongly affected the amphiphilicity of the short peptides and their interactions with different membranes. This work has revealed a strong relationship among side chain structures, amphiphilicity and selective bioactivities of the short peptide amphiphiles.
Co-reporter:Shengjie Wang, Junyi Xue, Xin Ge, Haiming Fan, Hai Xu and Jian R. Lu
Chemical Communications 2012 - vol. 48(Issue 75) pp:NaN9417-9417
Publication Date(Web):2012/07/31
DOI:10.1039/C2CC34667B
By manipulating the interfacial interactions between the peptide templates and the silicate species derived from TEOS and APTES, a facile biomimetic method was developed for the fabrication of silica nanostructures exhibiting “string-of-beads” and fibrillar morphologies of varied sizes.
Co-reporter:
Analytical Methods (2009-Present) 2012 - vol. 4(Issue 1) pp:
Publication Date(Web):
DOI:10.1039/C1AY05495C
We demonstrate that by using constant wavelength synchronous fluorescence spectrometry (CW-SFS) critical concentrations of some types of aggregation can be quantified. Detection of aggregation associated with hydrogen bonding in Chlorin e6 and Triton X-100 suggest that CW-SFS may be a technique that can explore aggregation at much lower levels (dimer, trimer, oligomer, etc.)
Co-reporter:Meiwen Cao, Ningning Wang, Lei Wang, Yu Zhang, Yucan Chen, Zilong Xie, Zongyi Li, Elias Pambou, Ruiheng Li, Cuixia Chen, Fang Pan, Hai Xu, Jeffery Penny, John R. P. Webster and Jian R. Lu
Journal of Materials Chemistry A 2016 - vol. 4(Issue 1) pp:NaN161-161
Publication Date(Web):2015/11/18
DOI:10.1039/C5TB02065D
Different amphiphilic peptides were used to mediate the direct exfoliation of graphite into few-layered graphene flakes in aqueous solutions. Charge was found to be an important parameter in determining their graphite exfoliating efficiency. The anionic molecules were more favorable than the cationic ones leading to a higher efficiency. The gemini-type peptide IleIleIleCys–CysIleIleIle (I3C–CI3) exhibited the highest efficiency, which might be attributed to its specific physicochemical properties and interactions with graphene sheets. I3C–CI3 adsorbed onto the graphene surface as either monomers or self-assembled nanoaggregates. These adsorbed species increased both electrostatic and steric repulsions between the graphene/I3C–CI3 composites. More interestingly, the graphene/I3C–CI3 composites showed a reversible pH-dependent dispersion/aggregation. This behavior resulted from the pH-sensitive protonation of the peptide molecules and was rarely found in the graphene dispersions exfoliated by traditional surfactants. Moreover, the graphene/I3C–CI3 dispersion was used to fabricate free-standing macroscopic composite films that contained different nanostructures. The study expands the library of available agents for direct graphite exfoliation to produce graphene sheets. Employing peptide molecules as graphene exfoliating and stabilizing agents avoids the use of toxic reagents, which may allow fabrication of functional composite materials for biocompatible applications.
![2-{[(dodecyloxy)(hydroxy)phosphoryl]oxy}-N,N,N-trimethylethanaminium chloride](http://img.cochemist.com/ccimg/54000/53949-18-1.png)
![2-{[(dodecyloxy)(hydroxy)phosphoryl]oxy}-N,N,N-trimethylethanaminium chloride](http://img.cochemist.com/ccimg/54000/53949-18-1_b.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4_b.png)
![5H-Benzo[a]phenoxazin-5-one,9-(diethylamino)-](http://img.cochemist.com/ccimg/7400/7385-67-3.png)
![5H-Benzo[a]phenoxazin-5-one,9-(diethylamino)-](http://img.cochemist.com/ccimg/7400/7385-67-3_b.png)
![Hexadecanoic acid,1,1'-[1-[[[(2,3-dihydroxypropoxy)hydroxyphosphinyl]oxy]methyl]-1,2-ethanediyl]ester](http://img.cochemist.com/ccimg/4600/4537-77-3.png)
![Hexadecanoic acid,1,1'-[1-[[[(2,3-dihydroxypropoxy)hydroxyphosphinyl]oxy]methyl]-1,2-ethanediyl]ester](http://img.cochemist.com/ccimg/4600/4537-77-3_b.png)
![3,5,9-Trioxa-4-phosphapentacosan-1-aminium,4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-, inner salt, 4-oxide](http://img.cochemist.com/ccimg/2700/2644-64-6.png)
![3,5,9-Trioxa-4-phosphapentacosan-1-aminium,4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-, inner salt, 4-oxide](http://img.cochemist.com/ccimg/2700/2644-64-6_b.png)
