Direct visualisation of lipid bilayer cubic phases using Atomic Force Microscopy

Inverse bicontinuous cubic (Q(II)) phases are nanostructured materials formed by lipid self-assembly. We have successfully imaged thin films of hydrated Q(II) phases from two different systems using AFM. The images show periodic arrays of water channels with spacing and symmetry consistent with published SAXS data on the bulk materials.

Double-gyroid morphology of a polystyrene-block-poly(ferrocenylethylmethylsilane) diblock copolymer: a route to ordered bicontinuous nanoscale architectures

A polystyrene-block-poly(ferrocenylethylmethylsilane) diblock copolymer, displaying a double-gyroid morphology when self-assembled in the solid state, has been prepared with a PFEMS volume fraction phi(PFMS)=0.39 and a total molecular weight of 64 000 Da by sequential living anionic polymerisation. A block copolymer with a metal-containing block with iron and silicon in the main chain was selected due to its plasma etch resistance compared to the organic block. Self-assembly of the diblock copolymer in the bulk showed a stable, double-gyroid morphology as characterised by TEM. SAXS confirmed that the structure belonged to the Ia3d space group.

Biomimetic triblock copolymer membranes: from aqueous solutions to solid supports

In the present paper, we studied the preparation of biomimetic triblock copolymer (ABA) membranes in aqueous solution and their deposition into solid supports. The self-assembly structures of the ABA in aqueous solution was investigated by using optical microscopy, dynamic light scattering, electron microscopy (EM) and SAXS. Spherical and tubular polymersomes were found at the highest concentrations investigated. The mechanism of deposition on solid supports (mica and glass) was elucidated by using atomic force microscopy (AFM). The deposition results in the formation of a uniform defect-free membrane at suitable polymer concentrations.

Puroindoline-a, a lipid binding protein from common wheat, spontaneously forms prolate protein micelles in solution

The self-assembly in solution of puroindoline-a (Pin-a), an amphiphilic lipid binding protein from common wheat, was investigated by small angle neutron scattering, dynamic light scattering and size exclusion chromatography. Pin-a was found to form monodisperse prolate ellipsoidal micelles with a major axial radius of 112 +/- 4.5 A ˚ and minor axial radius of 40.4 +/- 0.18 A ˚ . These protein micelles were formed by the spontaneous self-assembly of 38 Pin-a molecules in solution and were stable over a wide pH range (3.5–11) and at elevated temperatures (20–65 degC). Pin-a micelles could be disrupted upon addition of the non-ionic surfactant dodecyl-b-maltoside, suggesting that the protein self-assembly is driven by hydrophobic forces, consisting of intermolecular interactions between Trp residues located within a well-defined Trp-rich domain of Pin-a.

Thiolated mucoadhesive and PEGylated nonmucoadhesive organosilica nanoparticles from 3-Mercaptopropyltrimethoxysilane

A novel approach has been developed to synthesize thiolated sub-100 nm organosilica nanoparticles from 3-mercaptopropyltrimethoxysilane (MPTS) through its self-condensation in dimethylsulfoxide in contact with atmospheric oxygen. The formation of MPTS nanoparticles proceeds through the condensation of methoxysilane groups and simultaneous disulfide bridging caused by partial oxidation of thiol groups. These nanoparticles showed excellent colloidal stability in dilute aqueous dispersions but underwent further self-assembly into chains and necklaces at higher concentrations. They exhibited very good ability to adhere to ocular mucosal surfaces, which can find applications in drug delivery. The thiolated nanoparticles could also be easily modified through PEGylation resulting in a loss of their mucoadhesive properties.

Biomimetic soft matter

Biomaterials are often soft materials. There is now growing interest in designing, synthesizing and characterising soft materials that mimic the properties of biological materials such as tissue, proteins, DNA or cells. Research on biomimetic soft matter is therefore a developing theme with important emerging applications in biomedicine including tissue engineering, diagnostics, gene therapy, drug delivery and many others. There are also important basic science questions concerning the use of concepts from colloid and polymer science to understand the self-assembly of biomimetic soft materials. This issue of Soft Matter presents a selection of extremely topical articles on a diversity of biomimetic soft matter systems. I thank the contributors for this quite remarkable collection of papers, which report many fascinating discoveries and insights.

Reversible thermal transition of polydiacetylene based on KTTKS collagen sequence

Here we explore the physico-chemical properties of a peptide amphiphile obtained by chemical conjugation of the collagenstimulating peptide KTTKS with 10,12-pentacosadiynoic acid which photopolymerizes as a stable and extended polydiacetylene. We investigate the self-assembly of this new polymer and rationalize its peculiar behavior in terms of a thermal conformational transition. Surprisingly, this polymer shows a thermal transition associated with a non-cooperative increase in b-sheet content at high temperature.

A new tetranuclear copper(II) complex with oximate bridges: structure, magnetic properties and DFT study

A new tetranuclear complex, [Cu4L4](ClO4)4·2H2O (1), has been synthesized from the self-assembly of copper(II) perchlorate and the tridentate Schiff base ligand (2E,3E)-3-(2-aminopropylimino) butan-2-one oxime (HL). Single-crystal X-ray diffraction studies reveal that complex 1 consists of a Cu4(NO)4 core where the four copper(II) centers having square pyramidal environment are arranged in a distorted tetrahedral geometry. They are linked together by a rare bridging mode (μ3-η1,η2,η1) of oximato ligands. Analysis of magnetic susceptibility data indicates moderate antiferromagnetic (J1 = −48 cm−1, J2 = −40 cm−1 and J3 = −52 cm−1) exchange interaction through σ-superexchange pathways (in-plane bridging) of the oxime group. Theoretical calculations based on DFT technique have been used to obtain the energy states of different spin configurations and estimate the coupling constants and to understand the exact magnetic exchange pathways.

The collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts

The collagen production of human dermal and corneal fibroblasts in contact with solutions of the peptide amphiphile (PA) C16–KTTKS is investigated and related to its self-assembly into nanotape structures. This PA is used in antiwrinkle cosmeceutical applications (trade name Matrixyl). We prove that C16–KTTKS stimulates collagen production in a concentration-dependent manner close to the critical aggregation concentration determined from pyrene fluorescence spectroscopy. This suggests that self-assembly and the stimulation of collagen production are inter-related.

Collagen stimulating effect of peptide amphiphile C16−KTTKS on human fibroblasts

The collagen production of human dermal and corneal fibroblasts in contact with solutions of the peptide amphiphile (PA) C16−KTTKS is investigated and related to its self-assembly into nanotape structures. This PA is used in antiwrinkle cosmeceutical applications (trade name Matrixyl). We prove that C16−KTTKS stimulates collagen production in a concentration-dependent manner close to the critical aggregation concentration determined from pyrene fluorescence spectroscopy. This suggests that self-assembly and the stimulation of collagen production are inter-related.

Coassembly in binary mixtures of peptide amphiphiles containing oppositely charged residues

The self-assembly in water of designed peptide amphiphile (PA) C16-ETTES containing two anionic residues and its mixtures with C16-KTTKS containing two cationic residues has been investigated. Multiple spectroscopy, microscopy, and scattering techniques are used to examine ordering extending from the β-sheet structures up to the fibrillar aggregate structure. The peptide amphiphiles both comprise a hexadecyl alkyl chain and a charged pentapeptide headgroup containing two charged residues. For C16-ETTES, the critical aggregation concentration was determined by fluorescence experiments. FTIR and CD spectroscopy were used to examine β-sheet formation. TEM revealed highly extended tape nanostructures with some striped regions corresponding to bilayer structures viewed edge-on. Small-angle X-ray scattering showed a main 5.3 nm bilayer spacing along with a 3 nm spacing. These spacings are assigned respectively to predominant hydrated bilayers and a fraction of dehydrated bilayers. Signs of cooperative self-assembly are observed in the mixtures, including reduced bundling of peptide amphiphile aggregates (extended tape structures) and enhanced β-sheet formation.

New RGD-peptide amphiphile mixtures containing a negatively charged diluent

Here, we studied the self-assembly of two peptide amphiphiles, C16-Gly-Gly-Gly-Arg-Gly- Asp (PA 1: C16-GGG-RGD) and C16-Gly-Gly-Gly-Arg-Gly-Asp-Ser (PA 2: C16-GGG-RGDS).We showed that PA 1 and PA 2 self-assemble into nanotapes with an internal bilayer structure. C16 chains were highly interdigitated within the nanotape cores, while the peptide blocks formed water-exposed b-sheets too. PA 1 nanotapes were characterized by one spacing distribution, corresponding to a more regular internal structure than that of PA 2 nanotapes, which presented two different spacing distributions. We showed that it is possible to obtain homogeneous nanotapes in water by co-assembling PA 1 or PA 2 with the negatively charged diluent C16-Glu-Thr-Thr-Glu- Ser (PA 3: C16-ETTES). The homogeneous tapes formed by PA 1–PA 3 or PA 2–PA 3 mixtures presented a structure similar to that observed for the corresponding pure PA 1 or PA 2 nanotapes. The mixed nanotapes, which were able to form a stabilized matrix containing homogeneously distributed cell adhesive RGD groups, represent promising materials for designing new cell adhesion substrates.

Tuning chelation by the surfactant-like peptide A6H using predetermined pH values

We examine the self-assembly of a peptide A6H comprising a hexa-alanine sequence A6 with a histidine (H) “head group”, which chelates Zn2+ cations. We study the self assembly of A6H and binding of Zn2+ ions in ZnCl2 solutions, under acidic and neutral conditions. A6H self-assembles into nanotapes held together by a β-sheet structure in acidic aqueous solutions. By dissolving A6H in acidic ZnCl2 solutions, the carbonyl oxygen atoms in A6H chelate the Zn2+ ions and allow for β-sheet formation at lower concentrations, consequently reducing the onset concentration for nanotape formation. A6H mixed with water or ZnCl2 solutions under neutral conditions produces short sheets or pseudocrystalline tapes, respectively. The imidazole ring of A6H chelates Zn2+ ions in neutral solutions. The internal structure of nanosheets and pseudocrystalline sheets in neutral solutions is similar to the internal structure of A6H nanotapes in acidic solutions. Our results show that it is possible to induce dramatic changes in the self-assembly and chelation sites of A6H by changing the pH of the solution. However, it is likely that the amphiphilic nature of A6H determines the internal structure of the self-assembled aggregates independent from changes in chelation.

Alanine-rich amphiphilic peptide containing the RGD cell adhesion motif: a coating material for human fibroblast attachment and culture

We studied the self-assembly of peptide A6RGD (A: alanine, R: arginine, G: glycine, D: aspartic acid) in water, and the use of A6RGD substrates as coatings to promote the attachment of human cornea stromal fibroblasts (hCSFs). The self-assembled motif of A6RGD was shown to depend on the peptide concentration in water, where both vesicle and fibril formation were observed. Oligomers were detected for 0.7 wt% A6RGD, which evolved into short peptide fibres at 1.0 wt% A6RGD, while a co-existence of vesicles and long peptide fibres was revealed for 2–15 wt% A6RGD. A6RGD vesicle walls were shown to have a multilayer structure built out of highly interdigitated A6 units, while A6RGD fibres were based on β-sheet assemblies. Changes in the self-assembly motif with concentration were reflected in the cell culture assay results. Films dried from 0.1–1.0 wt% A6RGD solutions allowed hCSFs to attach and significantly enhanced cell proliferation relative to the control. In contrast, films dried from 2.5 wt% A6RGD solutions were toxic to hCSFs.

Influence of elastase on alanine-rich peptide hydrogels

The self-assembly of the alanine-rich amphiphilic peptides Lys(Ala)6Lys (KA6K) and Lys(Ala)6Glu (KA6E)with homotelechelic or heterotelechelic charged termini respectively has been investigated in aqueous solution. These peptides contain hexa-alanine sequences designed to serve as substrates for the enzyme elastase. Electrostatic repulsion of the lysine termini in KA6K prevents self-assembly, whereas in contrast KA6E is observed, through electron microscopy, to form tape-like fibrils, which based on X-ray scattering contain layers of thickness equal to the molecular length. The alanine residues enable efficient packing of the side-chains in a beta-sheet structure, as revealed by circular dichroism, FTIR and X-ray diffraction experiments. In buffer, KA6E is able to form hydrogels at sufficiently high concentration. These were used as substrates for elastase, and enzyme-induced de-gelation was observed due to the disruption of the beta-sheet fibrillar network. We propose that hydrogels of the simple designed amphiphilic peptide KA6E may serve as model substrates for elastase and this could ultimately lead to applications in biomedicine and regenerative medicine.