Tunable, Temperature‐Responsive Polynorbornenes with Side Chains Based on an Elastin Peptide Sequence

Abstract

Natural mammalian elastin fibers are cross-linked networks of the protein tropoelastin, which functions as the primary component of human blood vessels. Extensive physical and theoretical studies on this protein have shed light on the mechanism behind its unique elasticity.[1] Tropoelastin is comprised of hydrophobic domains of the repeating amino acid sequence -(VPGVG) n -and domains rich in alanine and lysine residues for intermolecular cross-linking. The hydrophobic domains are conformationally dynamic, and the transition between random coils and tightly wound b sheets results in large changes in the hydration sphere of the protein. This process has been determined to be fundamental to the elasticity of the cross-linked networks.[2] In the absence of chain cross-linking, the change in conformation is manifested by a temperature-dependent phase transition known as a lower critical solution temperature (LCST), below which the protein is soluble and above which it is insoluble. To take advantage of the physical properties of tropoelastin, elastinlike polypeptides (ELPs) have been synthesized by microbial expression systems [3] and have been studied for use as biomaterials.[4] The promise presented by ELPs has inspired us to search for readily accessible synthetic derivatives of these proteins for the development of new materials that promote endothelial cell growth. We hoped to incorporate the elastin amino acid sequence -(VPGVG)-as the side chain on biomimetic polynorbornenes to obtain a synthetic polymer that exhibits the phase-transition behavior of its polypeptide model.The research groups of van Hest and Cameron have demonstrated that polymers with the -(VPGVG)-elastin sequence as a side chain exhibit LCSTs that are dependent on the concentration, degree of polymerization, and the pH value. [5,6] The polymers were synthesized by using controlled radical polymerization methods to form either ABA block copolymers with low degrees of polymerization (DP < 12) [5] or homopolymers with higher DP values. [6] Recently, Setton and co-workers have shown that dimeric repeat units of -(VPGVG)-attached to norbornene monomers could be polymerized by using ring-opening metathesis polymerization (ROMP) with [(H 2 IMes)(PCy 3 )(Cl) 2 Ru = CHPh] (Mes = 2,4,6-trimethylphenyl, Cy = cyclohexyl) as an initiator. The oligomers (DP < 12) produced exhibited temperature-dependent phase transitions. [7] The LCSTs in most synthetic elastin-based materials are strongly dependent on the overall molecular weight of the polymer. Limitations in the synthetic methods used for their assembly have meant that high-molecular-weight elastinbased polymers have not been investigated. Our goal was to develop a robust method to synthesize elastin-based polymers in which the LCST was not molecular-weight dependent and could be tuned for any targeted application. We anticipated that by making random copolymers of an elastin-based monomer and a hydrophilic polyethylene glycol (PEG) based monomer by ROMP, the LCST could be manipulated through the ratio ...

Synthesis and Postpolymerization Modification of Thermoresponsive Coatings Based on Pentaerythritol Monomethacrylate: Surface Analysis, Wettability, and Protein Adsorption

“…17 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 [7,8,[21][22][23]37], has never been reported before for PPM. Temperature sensitivity of similar systems was observed for poly(2-hydroxyethyl methacrylate)s or poly(2-hydroxypropyl acrylate)s [9][10][11], where the effect of molecular weight on both water solubility and LCST behavior was reported [9,38,39].…”

Recent advances in ring-opening metathesis polymerization, and application to synthesis of functional materials

“…53 The lower critical solution temperatures of copolymer 19, which is composed of an elastin-based monomer and a hydrophilic polyethylene glycol (PEG)-based monomer, are independent of molecular weights and tunable for target applications. 54 Several attempts have been made to incorporate PEG units into ROMP copolymers, including postpolymerization loading of an amphiphilic ROMP copolymer with a high-density peptide sequence 55 with PEG incorporated as part of the hydrophilic block. The block copolymerization of a norbornene derivative having a short peptide with a norbornene having a PEG substituent gives block copolymer 20, consisting of a segment with hydrophilic PEG side chains and a segment with more hydrophobic peptide side chains (Scheme 14).…”

Modular Design in Natural and Biomimetic Soft Materials

“…By adjusting the solvent mixture to avoid aggregation, Conrad and Grubbs were able to obtain high-molecular-weight VPGVG/ PEG 4 side-chain copolymers. [109] The authors were able to linearly adjust the solvent/self-interaction parameters, and hence the LCST, by random incorporation of the two sidechain monomers in various ratios.…”