The addition of amines to an aldehyde surfactant, which was designed to be analogous to didodecyldimethylammonium bromide, gave exchangeable “iminolipids” that self-assembled to give stable aqueous dispersions of nano-sized vesicles. For example, sonication of suspensions of the n-hexylamine-derived iminolipid gave vesicles 50 to 200 nm in diameter that could encapsulate a water-soluble dye. The iminolipids could undergo dynamic exchange with added amines, and the resulting equilibrium constants (Krel) were quantified by 1H NMR spectroscopy. In the absence of lipid self-assembly, in CDCl3, the assayed primary amines gave very similar Krel values. However in D2O the value of Krel generally increased with increasing amine hydrophobicity, consistent with partitioning into a self-assembled bilayer. Amines with aromatic groups showed significantly higher values of Krel in D2O compared to similarly hydrophobic alkylamines, suggesting that π–π interactions favor lipid self-assembly. Given this synergistic relationship, π-rich pyrenyliminolipids were created and used to exfoliate graphite, leading to aqueous dispersions of graphene flakes that were stable over several months.

Two complementary β-sheet-forming decapeptides have been created that form binary self-repairing hydrogels upon combination of the respective free-flowing peptide solutions at pH 7 and >0.28 wt%. The component peptides showed little structure separately but formed extended β-sheet fibres upon mixing, which became entangled to produce stiff hydrogels. Microscopy revealed two major structures; thin fibrils with a twisted or helical appearance and with widths comparable to the predicted lengths of the peptides within a β-sheet, and thicker, longer, interwoven fibres that appear to comprise laterally-packed fibrils. A range of gel stiffnesses (G′ from 0.05 to 100 kPa) could be attained in this system by altering the assembly conditions, stiffnesses that cover the rheological properties desirable for cell culture scaffolds. Doping in a RGD-tagged component peptide at 5 mol% improved 3T3 fibroblast attachment and viability compared to hydrogel fibres without RGD functionalisation.

The synthetic biology toolbox lacks extendable and conformationally controllable yet easy-to-synthesize building blocks that are long enough to span membranes. To meet this need, an iterative synthesis of α-aminoisobutyric acid (Aib) oligomers was used to create a library of homologous rigid-rod 310-helical foldamers, which have incrementally increasing lengths and functionalizable N- and C-termini. This library was used to probe the inter-relationship of foldamer length, self-association strength, and ionophoric ability, which is poorly understood. Although foldamer self-association in nonpolar chloroform increased with length, with a ∼14-fold increase in dimerization constant from Aib6 to Aib11, ionophoric activity in bilayers showed a stronger length dependence, with the observed rate constant for Aib11 ∼70-fold greater than that of Aib6. The strongest ionophoric activity was observed for foldamers with >10 Aib residues, which have end-to-end distances greater than the hydrophobic width of the bilayers used (∼2.8 nm); X-ray crystallography showed that Aib11 is 2.93 nm long. These studies suggest that being long enough to span the membrane is more important for good ionophoric activity than strong self-association in the bilayer. Planar bilayer conductance measurements showed that Aib11 and Aib13, but not Aib7, could form pores. This pore-forming behavior is strong evidence that Aibm (m ≥ 10) building blocks can span bilayers.

A simple synthetic route has been devised for the production of coating agents that can give multivalent displays of saccharides on the surface of magnetite nanoparticles and phospholipid vesicles. A versatile and potentially high-throughput condensation reaction allowed the rapid synthesis of a variety of glycosylhydrazide conjugates with lipid, resorcinol or catechol termini, each in good yield and high anomeric purity. The hydrolytic stability of these adducts was assessed in D2O at different pD values using 1H-NMR spectroscopy, whilst quartz crystal microbalance with dissipation monitoring (QCM-D) confirmed that the saccharide functionality on bilayers and on nanoparticles was still available to lectins. These multivalent saccharide displays promoted nanoparticle interactions with cells, for example N-acetylglucosamine-coated nanoparticles interacted much more effectively with 3T3 fibroblasts than uncoated nanoparticles with these cells. Despite potential sensitivity to oxidation, catechol coatings on magnetite nanoparticles were found to be more stable and generate better nanoparticle interactions with fibroblasts than resorcinol coatings.

Helical peptide foldamers rich in α-aminoisobutyric acid (Aib) act as peptaibol-mimicking ionophores in the phospholipid bilayers of artificial vesicles. Racemic samples of these foldamers are more active than their enantiopure counterparts, which was attributed to differing propensities to form aggregates with crystal-like features in the bilayer.

The magnetic release of catalytically active enzymes from vesicular compartments within aggregated nanomaterials has been demonstrated. These nanomaterials, magnetic nanoparticle-vesicle aggregates (MNPVs), were formed by the self-assembly of biotinylated silica-coated Fe3O4 nanoparticles, biotinylated vesicles and tetrameric avidin. The unique features of nanoscale magnetite allow adhesion between membranes to be combined with magnetically triggered transit of reagents across membranes. Adding short spacers between the adhesive biotin groups and the nanoparticle or vesicle surfaces was found to strengthen binding to avidin, with binding of avidin to biotinylated bilayers and biotinylated nanoparticles monitored by quartz crystal microgravimetry with dissipation (QCM-D). Three different reagents were released from the vesicle compartments of MNPVs by a pulse of alternating magnetic field, with the release of a dye modelling the release of small molecule substrates, and the release of cytochrome c modelling the release of biological polymers, such as enzymes. To confirm that enzymes could be released and maintain activity, trypsin was encapsulated and shown to digest casein after magnetically triggered release.

The effect of Schellman motifs on the adoption of stable 310 helical conformations in a series of aminoisobutyric (Aib) oligomers has been studied in the solid state and solution. The destabilising effect of the Schellman motif (a local inversion of helical screw-sense due to a C-terminal ester residue) was quantified in the solid state using X-ray crystallography through analysis of the torsion angles and their deviation from those observed in an ideal 310 helix. Investigation of the intramolecular hydrogen-bonding interactions in the solid state led to the identification of a fully extended C5 conformation in one oligomer, which is a novel folding motif for Aib oligomers. The effect of ester groups with differing steric demands on intermolecular hydrogen-bonding contacts in the solid state was also ascertained. In solution, the adoption of a 310 conformation in Aib oligomers appeared to be more finely tuned, depending on a number of factors, including chain length and the steric demands of the C-terminal destabilising Schellman motif.

Wulff-type boronic acids have been shown to act as ionophores at pH 8.2 by transporting Na+ through phospholipid bilayers. A cholate–boronic acid conjugate was synthesised and shown to be an ionophore, although the hydroxyl-lined face of the cholate moiety did not enhance ion transport. Mechanistic studies suggested a carrier mechanism for Na+ transport. The addition of fructose (>5 mM) strongly inhibited ionophoric activity of the cholate–boronic acid conjugate, mirrored by a strong decrease in the ability of this compound to partition into an organic phase. Modelling of the partitioning and ion transport data, using a fructose/boronic acid binding constant measured at pH 8.2, showed a good correlation with the extent of fructose/boronic acid complexation and suggested high polarity fructose/boronic acid complexes are poor ionophores. The sensitivity of ion transport to fructose implies that boronic acid-based antibiotic ionophores with activity modulated by polysaccharides in the surrounding environment may be accessible.

A synthetic perfluoroalkyl-tagged lactosyl glycolipid has been shown to form lipid microdomains in fluid phospholipid bilayers. When embedded in the membranes of phospholipid vesicles, this glycolipid was trans-sialylated by soluble T. cruzi trans-sialidase (TcTS) to give a perfluoroalkyl-tagged glycolipid that displayed the ganglioside GM3 epitope, with up to 35% trans-sialylation from fetuin after 18 h. Following sialylation, vesicles bearing this Neu5Ac(α2-3)Gal(β1-4)Glc sequence in their “glycocalyx” were recognised and agglomerated by the lectin M. amurensis leukoagglutinin. Monitoring TcTS-mediated trans-sialylation by HPLC over the first 6 h revealed that enzymatic transformation of bilayer-embedded substrate was much slower than that of a soluble lactosyl substrate. Furthermore, clustering of the lactose-capped glycolipid into “acceptor” microdomains did not increase the rate of sialic acid transfer from fetuin by soluble TcTS, instead producing slight inhibition.

Cells carefully control the transit of compounds through their membranes using “gated” protein channels that respond to chemical stimuli. Connexin gap junctions, which are high conductance cell-to-cell channels, are a remarkable class of “gated” channel with multiple levels of assembly. A gap junction between adhering cells comprises two half-channels in each cell membrane that adhere to each other to form a continuous cell-to-cell channel. Each half-channel is a hexameric assembly of six protein transmembrane subunits. These gap junctions display both intramembrane assembly and intermembrane assembly, making them an attractive target for biomimetic studies. Although many examples of self-assembled channels have been developed, few can also mediate intermembrane adhesion. Developing systems that combine membrane adhesion with controlled transit across the membrane would not only provide a better understanding of self-assembly in and around the membrane, but would also provide a route towards smart biomaterials, targeted drug delivery and an interface with nanotechnology.This Account describes our biomimetic approaches to combining membrane adhesion with membrane transport, using both self-assembled “sticky” pores and “sticky” nanoparticles to trigger transit across membranes. This combination links both fundamental and applied research, acting as a bridge between molecular level assembly and the formation of functional biomaterials. The ultimate goal is to create complex self-assembled systems in biological or biomimetic environments that can both interface with cells and transport compounds across bilayers in response to remote chemical or electromagnetic signals. Our research in this area started with fundamental studies of intramembrane and intermembrane self-assembly, building upon previously known channel-forming compounds to create self-assembled channels that were switchable or able to mediate vesicle–vesicle adhesion. Subsequently, nanoparticles with a “sticky” coating were used to mediate adhesion between vesicles. Combining these adhesive properties with the unique characteristics of nanosized magnetite allowed a noninvasive magnetic signal to trigger transport of compounds out of magnetic nanoparticle-vesicle assemblies. Adding an extravesicular matrix produced new responsive biomaterials for use in tissue engineering. These biomaterials can be magnetically patterned and can deliver drugs upon receipt of a magnetic signal, allowing spatiotemporal control over cellular responses.

A self-assembled Fmoc-peptide hydrogel has been interfaced with a liquid crystal (LC) display to give an optical sensor for enzyme activity. An Fmoc-TL-OMe hydrogel was selected as it can be formed in situ by enzyme-mediated assembly with thermolysin, and undergoes enzyme-mediated diassembly upon subtilisin addition. This enzyme-responsive hydrogel provides a semi-rigid, highly hydrated and biocompatible environment that also holds the LC display in place. A dual layer design was developed, where a phospholipid-loaded upper gel layer was separated from the LC display by a phospholipid free lower layer. Subtilisin (0.15 μM) digested both layers to give a gel-to-sol transition after several hours that liberated the phospholipid and produced a light-to-dark optical change in the LC display. The optical response was dependent upon the gel-to-sol transition; elastase or common components of serum did not disassemble the Fmoc-TL-OMe hydrogel and did not give an optical response.

Magnetically patterned and responsive biomaterials have been shown to produce spatially controlled cell death in response to a magnetic signal. The responsive elements in these nano-structured biomaterials are magnetic nanoparticle-vesicle assemblies (MNPVs), which are thermally sensitive vesicles crosslinked by magnetic nanoparticles. MNPVs are nano-sized drug delivery platforms that are responsive to magnetic fields in two ways: they can be spatially manipulated by static magnetic fields, and upon exposure to an alternating magnetic field (AMF) they can release chemical messengers stored within the vesicles. Magnetically initiated release of nickel(II) from MNPVs immobilised in an alginate hydrogel was used to produce remotely triggered and spatially controlled apoptosis of fibroblasts cultured in the hydrogel. The ability to manipulate MNPVs with static magnetic fields was used to immobilise the MNPVs in only one region of the biomaterial; subsequent AMF-induced release of nickel(II) caused a wave of cellular apoptosis through the biomaterial as the nickel(II) slowly diffused through the hydrogel.

Creating tissue-mimetic biomaterials able to deliver bioactive compounds after receipt of a remote and non-invasive trigger has so far proved to be challenging. The possible applications of such “smart” biomaterials are vast, ranging from subcutaneous drug delivery to tissue engineering. Self-assembled phospholipid vesicles (liposomes) have the ability to deliver both hydrophilic and hydrophobic drugs, and controlling interactions between functionalized vesicles and cells within biomaterials is an important step for targeted drug delivery to cells. We report an investigation of the interactions between thermally-sensitive and biotin-coated dipalmitoyl phosphatidylcholine vesicles and 3T3 fibroblast cells. The stability of these vesicles under physiological conditions was assessed and their interaction with the cell membranes of fibroblasts in media and alginate/fibronectin mixtures was studied. Stable vesicle-cell aggregates were formed in fluid matrices, and could be a model system for improving the delivery of remotely released drugs within vesicle-containing biomaterials.

Magnetic nanoparticle–vesicle assemblies embedded within a hydrogel extravesicular matrix have been shown to release their contents in response to a remote magnetic trigger.

Mannosyl glycolipids with perfluoroalkyl membrane anchors have been synthesised. When inserted into vesicles, these mannosyl lipids either dispersed evenly over the surface or, in the presence of cholesterol, phase-separated into artificial lipid rafts. At 1% mol/mol, the affinity of dispersed mannosyl lipids for Con A was 3-fold weaker than in solution, perhaps reflecting steric blocking by the surface. However increasing membrane loading 5-fold increased Con A affinity by up to 75% and indicated weak intramembrane chelation of Con A. Despite this observation, concentrating the mannosyl lipids into artificial lipid rafts did not significantly improve affinity for Con A. This lack of a cluster glycoside effect was ascribed to lipid congestion inhibiting intra-raft chelation of Con A, and implies that glycolipids located in lipid rafts may not necessarily be preorganised for multivalent binding.

Vesicles (liposomes) have been shown to be excellent vehicles for drug delivery, yet assemblies of vesicles (vesicle aggregates) have been used infrequently in this context. However vesicle assemblies have useful properties not available to individual vesicles; their size can cause localisation in specific tissues and they can incorporate more functionality than is possible with individual vesicles. This article reviews progress on controlling the properties of vesicle assemblies in vitro, applications of vesicle assemblies in vivo, and our recent creation of magnetic nanoparticle–vesicle assemblies. The latter assemblies contain vesicles crosslinked by coated Fe3O4 nanoparticles and this inclusion of magnetic functionality makes them magnetically responsive, potentially allowing magnetically-induced contents release. This article describes further studies on the in vitro formation of these magnetic nanoparticle–vesicle assemblies, including the effect of changing magnetic nanoparticle concentration, pH, adhesive lipid structure and bilayer composition. These investigations have led to the development of thermally-sensitive magnetic nanoparticle–vesicle assemblies that release encapsulated methotrexate on warming.

A hydrogel-based sensor for screening protease specificity has been developed that combines the versatility of solid-phase synthesis (SPS) with the simplicity of liquid crystal display (LCD) technology.

A simple ion channel has been developed that can be created or disassembled through the addition or removal of palladium(II).

In an effort to improve the stability of our tissue-mimetic vesicle aggregates, we have investigated how increasing the valency of our multivalent crosslinking ligand, poly-L-histidine, affected both the extent of vesicle aggregation and the affinity of the multivalent ligand for the synthetic receptor Cu(1) embedded in the vesicle membranes. Although increasing ligand valency gave the anticipated increase in the size of the vesicle aggregates, isothermal calorimetric studies did not show the expected increase in the valence-corrected binding constant for the embedded receptors. To explain both observations, we have developed a simple new binding model that encompasses both multivalent binding to receptors on a single vesicle surface (intramembrane binding) and vesicle crosslinking (intermembrane binding).

To probe the effect of lipid fluorination on the formation of lipid domains in phospholipid bilayers, several new fluorinated and non-fluorinated synthetic lipids were synthesised, and the extent of phase separation of these lipids from phospholipid bilayers of different compositions was determined. At membrane concentrations as low as 1% mol/mol, both fluorinated and non-fluorinated lipids were observed to phase separate from a gel-phase (solid ordered) phospholipid matrix, but bilayers in a liquid disordered state caused no phase separation; if the gel-phase samples were heated above the transition temperature, then phase separation was lost. We found incorporation of perfluoroalkyl groups into the lipid enhanced phase separation, to such an extent that phase separation was observed from cholesterol containing bilayers in the liquid ordered phase.

Vesicles incorporating a fluorescent metal-chelating lipid can be linked together by addition of copper(II) and poly-L-histidine, but the stability of adhering vesicles towards fusion depends upon membrane composition.

A simple ion channel has been developed that can be created or disassembled through the addition or removal of palladium(II).

A hydrogel-based sensor for screening protease specificity has been developed that combines the versatility of solid-phase synthesis (SPS) with the simplicity of liquid crystal display (LCD) technology.

Wulff-type boronic acids have been shown to act as ionophores at pH 8.2 by transporting Na+ through phospholipid bilayers. A cholate–boronic acid conjugate was synthesised and shown to be an ionophore, although the hydroxyl-lined face of the cholate moiety did not enhance ion transport. Mechanistic studies suggested a carrier mechanism for Na+ transport. The addition of fructose (>5 mM) strongly inhibited ionophoric activity of the cholate–boronic acid conjugate, mirrored by a strong decrease in the ability of this compound to partition into an organic phase. Modelling of the partitioning and ion transport data, using a fructose/boronic acid binding constant measured at pH 8.2, showed a good correlation with the extent of fructose/boronic acid complexation and suggested high polarity fructose/boronic acid complexes are poor ionophores. The sensitivity of ion transport to fructose implies that boronic acid-based antibiotic ionophores with activity modulated by polysaccharides in the surrounding environment may be accessible.

The effect of Schellman motifs on the adoption of stable 310 helical conformations in a series of aminoisobutyric (Aib) oligomers has been studied in the solid state and solution. The destabilising effect of the Schellman motif (a local inversion of helical screw-sense due to a C-terminal ester residue) was quantified in the solid state using X-ray crystallography through analysis of the torsion angles and their deviation from those observed in an ideal 310 helix. Investigation of the intramolecular hydrogen-bonding interactions in the solid state led to the identification of a fully extended C5 conformation in one oligomer, which is a novel folding motif for Aib oligomers. The effect of ester groups with differing steric demands on intermolecular hydrogen-bonding contacts in the solid state was also ascertained. In solution, the adoption of a 310 conformation in Aib oligomers appeared to be more finely tuned, depending on a number of factors, including chain length and the steric demands of the C-terminal destabilising Schellman motif.

The magnetic release of catalytically active enzymes from vesicular compartments within aggregated nanomaterials has been demonstrated. These nanomaterials, magnetic nanoparticle-vesicle aggregates (MNPVs), were formed by the self-assembly of biotinylated silica-coated Fe3O4 nanoparticles, biotinylated vesicles and tetrameric avidin. The unique features of nanoscale magnetite allow adhesion between membranes to be combined with magnetically triggered transit of reagents across membranes. Adding short spacers between the adhesive biotin groups and the nanoparticle or vesicle surfaces was found to strengthen binding to avidin, with binding of avidin to biotinylated bilayers and biotinylated nanoparticles monitored by quartz crystal microgravimetry with dissipation (QCM-D). Three different reagents were released from the vesicle compartments of MNPVs by a pulse of alternating magnetic field, with the release of a dye modelling the release of small molecule substrates, and the release of cytochrome c modelling the release of biological polymers, such as enzymes. To confirm that enzymes could be released and maintain activity, trypsin was encapsulated and shown to digest casein after magnetically triggered release.

A synthetic perfluoroalkyl-tagged lactosyl glycolipid has been shown to form lipid microdomains in fluid phospholipid bilayers. When embedded in the membranes of phospholipid vesicles, this glycolipid was trans-sialylated by soluble T. cruzi trans-sialidase (TcTS) to give a perfluoroalkyl-tagged glycolipid that displayed the ganglioside GM3 epitope, with up to 35% trans-sialylation from fetuin after 18 h. Following sialylation, vesicles bearing this Neu5Ac(α2-3)Gal(β1-4)Glc sequence in their “glycocalyx” were recognised and agglomerated by the lectin M. amurensis leukoagglutinin. Monitoring TcTS-mediated trans-sialylation by HPLC over the first 6 h revealed that enzymatic transformation of bilayer-embedded substrate was much slower than that of a soluble lactosyl substrate. Furthermore, clustering of the lactose-capped glycolipid into “acceptor” microdomains did not increase the rate of sialic acid transfer from fetuin by soluble TcTS, instead producing slight inhibition.

In an effort to improve the stability of our tissue-mimetic vesicle aggregates, we have investigated how increasing the valency of our multivalent crosslinking ligand, poly-L-histidine, affected both the extent of vesicle aggregation and the affinity of the multivalent ligand for the synthetic receptor Cu(1) embedded in the vesicle membranes. Although increasing ligand valency gave the anticipated increase in the size of the vesicle aggregates, isothermal calorimetric studies did not show the expected increase in the valence-corrected binding constant for the embedded receptors. To explain both observations, we have developed a simple new binding model that encompasses both multivalent binding to receptors on a single vesicle surface (intramembrane binding) and vesicle crosslinking (intermembrane binding).

Mannosyl glycolipids with perfluoroalkyl membrane anchors have been synthesised. When inserted into vesicles, these mannosyl lipids either dispersed evenly over the surface or, in the presence of cholesterol, phase-separated into artificial lipid rafts. At 1% mol/mol, the affinity of dispersed mannosyl lipids for Con A was 3-fold weaker than in solution, perhaps reflecting steric blocking by the surface. However increasing membrane loading 5-fold increased Con A affinity by up to 75% and indicated weak intramembrane chelation of Con A. Despite this observation, concentrating the mannosyl lipids into artificial lipid rafts did not significantly improve affinity for Con A. This lack of a cluster glycoside effect was ascribed to lipid congestion inhibiting intra-raft chelation of Con A, and implies that glycolipids located in lipid rafts may not necessarily be preorganised for multivalent binding.

A membrane-spanning bis(meso-3-pyridyl) porphyrin 1 has been synthesized, embedded in EYPC vesicles, and upon Pd(II) addition has been shown to form ionophores that allow the passage of anionic 5/6-carboxyfluorescein through membranes. The geometric matching of bis(meso-3-pyridyl) porphyrin 1 and trans-Pd(II) was designed to give a cyclic porphyrin trimer [PdCl2(1)]3. However, solution-phase studies showed that PdCl2(PhCN)2 cross linked 1 into linear oligomers at porphyrin concentrations above 10 mM, although the formation of cyclic species was inferred from studies at concentrations below 2 μM. Fluorescence titrations showed that embedding porphyrin 1 in bilayers greatly reduced its affinity for Pd(II), but the combination of porphyrin 1 and Pd(II) gave an ionophoric species that increased the rate of 5/6-carboxyfluorescein (5/6-CF) transit through the phospholipid bilayer 12-fold. A maximum in the 5/6-CF release rate was observed at a Pd(II) concentration of 4 μM, and the application of a solution-phase binding model to the membrane phase showed that this peak in ionophoric activity corresponded to the greatest extent of porphyrin oligomerization. Further studies suggested these Pd(II)/porphyrin oligomers transported 5/6-CF via a channel mechanism.

A simple synthetic route has been devised for the production of coating agents that can give multivalent displays of saccharides on the surface of magnetite nanoparticles and phospholipid vesicles. A versatile and potentially high-throughput condensation reaction allowed the rapid synthesis of a variety of glycosylhydrazide conjugates with lipid, resorcinol or catechol termini, each in good yield and high anomeric purity. The hydrolytic stability of these adducts was assessed in D2O at different pD values using 1H-NMR spectroscopy, whilst quartz crystal microbalance with dissipation monitoring (QCM-D) confirmed that the saccharide functionality on bilayers and on nanoparticles was still available to lectins. These multivalent saccharide displays promoted nanoparticle interactions with cells, for example N-acetylglucosamine-coated nanoparticles interacted much more effectively with 3T3 fibroblasts than uncoated nanoparticles with these cells. Despite potential sensitivity to oxidation, catechol coatings on magnetite nanoparticles were found to be more stable and generate better nanoparticle interactions with fibroblasts than resorcinol coatings.

Magnetic nanoparticle–vesicle assemblies embedded within a hydrogel extravesicular matrix have been shown to release their contents in response to a remote magnetic trigger.

The addition of amines to an aldehyde surfactant, which was designed to be analogous to didodecyldimethylammonium bromide, gave exchangeable “iminolipids” that self-assembled to give stable aqueous dispersions of nano-sized vesicles. For example, sonication of suspensions of the n-hexylamine-derived iminolipid gave vesicles 50 to 200 nm in diameter that could encapsulate a water-soluble dye. The iminolipids could undergo dynamic exchange with added amines, and the resulting equilibrium constants (Krel) were quantified by 1H NMR spectroscopy. In the absence of lipid self-assembly, in CDCl3, the assayed primary amines gave very similar Krel values. However in D2O the value of Krel generally increased with increasing amine hydrophobicity, consistent with partitioning into a self-assembled bilayer. Amines with aromatic groups showed significantly higher values of Krel in D2O compared to similarly hydrophobic alkylamines, suggesting that π–π interactions favor lipid self-assembly. Given this synergistic relationship, π-rich pyrenyliminolipids were created and used to exfoliate graphite, leading to aqueous dispersions of graphene flakes that were stable over several months.

Helical peptide foldamers rich in α-aminoisobutyric acid (Aib) act as peptaibol-mimicking ionophores in the phospholipid bilayers of artificial vesicles. Racemic samples of these foldamers are more active than their enantiopure counterparts, which was attributed to differing propensities to form aggregates with crystal-like features in the bilayer.