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Mechanical responsiveness is essential to all biological systems down to the level of tissues and cells. The intra- and extracellular mechanics of such systems are governed by a series of proteins, such as microtubules, actin, intermediate filaments and collagen. As a general design motif, these proteins self-assemble into helical structures and superstructures that differ in diameter and persistence length to cover the full mechanical spectrum. Gels of cytoskeletal proteins display particular mechanical responses (stress stiffening) that until now have been absent in synthetic polymeric and low-molar-mass gels. Here we present synthetic gels that mimic in nearly all aspects gels prepared from intermediate filaments. They are prepared from polyisocyanopeptides grafted with oligo(ethylene glycol) side chains. These responsive polymers possess a stiff and helical architecture, and show a tunable thermal transition where the chains bundle together to generate transparent gels at extremely low concentrations. Using characterization techniques operating at different length scales (for example, macroscopic rheology, atomic force microscopy and molecular force spectroscopy) combined with an appropriate theoretical network model, we establish the hierarchical relationship between the bulk mechanical properties and the single-molecule parameters. Our results show that to develop artificial cytoskeletal or extracellular matrix mimics, the essential design parameters are not only the molecular stiffness, but also the extent of bundling. In contrast to the peptidic materials, our polyisocyanide polymers are readily modified, giving a starting point for functional biomimetic hydrogels with potentially a wide variety of applications, in particular in the biomedical field.

The design and synthesis of functional biomimetic water soluble polymers with a defined secondary structure has been developed using β-sheet polyisocyanopeptide scaffolds. Water soluble isocyanopolymers were prepared by random copolymerisation of the azido functionalized isocyanopeptides with nonfunctionalised methyl ester isocyanides derived from alanine. Upon saponification of the latter function a rigid rod water soluble polymer was obtained with an accessible azide for postfunctionalization. The potential of these biomimetic polymers was successfully demonstrated by using the click chemistry reaction of these polymers with an acetylene functionalised rhodamine dye.

Contains fulltext : 36533.pdf (Publisher’s version ) (Closed access) Rigid rod polyisocyanopeptides have been synthesised containing acetylene groups on the side arms as scaffolds for multifunctional derivatisation by the copper-catalysed click reaction between an acetylene and an azide. All materials were characterised in detail by spectroscopic procedures and for the processable polymers, atomic force microscopy was used to determine the molecular weight parameters. The solubility properties of the synthesised macromolecules are very dependent on the stereochemistry and/or the presence of solubilising trimethylsilyl groups on the acetylene function. The potential for derivatisation of the acetylene-containing materials using click chemistry was successfully demonstrated by the reaction of these polymers with aliphatic tails functionalised with azide moieties.

This contribution describes the synthesis and full characterization of oligo(ethylene glycol) functionalized polyisocyanopeptides. The thermal behavior of the resulting semi-flexible polymers was investigated in diluted aqueous conditions and features a tunable Lower Critical Solution Temperature (LCST). In line with previously described oligo(ethylene glycol) decorated polymers, the LCST of the materials shows a very small hysteresis effect and directly correlates with the oligo(ethylene glycol) side-chains length; short oligo(ethylene glycol) substituents are associated with lower LCST. In contrast with poly[oligo(ethylene glycol) methacrylate], a significant effect of the degree of polymerization (DP) of the poly(isocyanopeptide) core on the LSCT of the materials was observed. Most remarkably, poly(isocyanopeptide)-graft-oligo(ethylene glycol) chains of high DP lead to the reversible formation of strong hydrogels above the transition temperature, even at very low polymer concentration (0.1 wt.%). AFM studies point towards the formation of a highly organized fibrillar network in the gel-state, reminiscent of structures observed for low molecular weight gelators, polysaccharides, and protein-based (hydro)gels. It is proposed that the stiff and well-defined helical poly(isocyanopeptide) backbone avoids the collapse of the chains into globules at the transition temperature as usually observed for more flexible systems. Thus, above a critical DP the semi-flexible non-linear PEGs chains are getting kinetically trapped in an extended fibrillar network, when the oligo(ethylene glycol) corona hydrophilicity is lowered at higher temperature. As a result these polymers exhibit a strong ability to gel water at extremely low polymer concentrations.

Polyisocyanopeptides have been synthesised containing acetylene groups on the side arms as scaffolds for multifunctional derivatisation by the copper-catalysed click reaction with a variety of azides. By using ethylene glycol azide and perylene azide chromophoric water-soluble polymeric nanowires (Mw 1–2 million Daltons) were formed. The potential to incorporate multiple chromophores was also demonstrated by the reaction of the acetylene-containing polymers with perylene azide and azidocoumarin dyes. In the latter case a blue-shifted emission of the coumarin was observed due to the interaction with the coupled perylene molecules. In particular the ability to form water-soluble dye-containing polymers, which can be modified by the addition of biomolecules, such as antibodies, proteins and peptides, give materials that are very promising as novel biomarker materials.