Unraveling On-demand Strain-Stiffening in Nanofibrous Peptide–Polymer Conjugates to Mimic Contractility in Actinomyosin Networks

Abstract

Reinforcement owing to inner stress formation is of supreme importance in life and is the basis for biomechanical pathways, especially in the contractile materials resembling muscles. Cells strengthen their contiguous matrix by pulling thin actin filaments associated with bundles of myosin with molecular motors promoting rapid fluidization and dynamic stiffening of the cytoskeleton. Herein, we demonstrate an elegant synthetic design of a peptide−polymer conjugate network that exhibits multiple hierarchical control over its stiffening. Dynamic Schiff base crosslinking of semi-flexible peptide nanofibers with the thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) copolymer endows a covalent network. Further, the photo-dimerizable 4-methylcoumarin moieties at the core of peptide nanofibers can also be reversibly photo-fixated with the choice of light. The conjugates exhibit macroscopic heatstiffening response by generating inner stress through a coil-to-globule transition owing to the lower critical solution temperature of PNIPAM. Moreover, the covalently crosslinked network noticeably stiffens in response to applied shear stress that can be further ramped up in the photo-fixated peptide nanofibers. Finally, an excellent biocompatibility toward U2OS cell lines validates these as ideal biomimetic and adaptive materials. Overall, we report for the first time a synthetic strain-stiffening network based on a nonequilibrium self-assembled peptide fiber toward non-linear biomechanics analogous to the actinomyosin network ubiquitous in cells and tissues.

Post-Implantation Stiffening by a Bioinspired, Double-Network, Self-Healing Hydrogel Facilitates Minimally Invasive Cell Delivery for Cartilage Regeneration

“…The collapse of the interpenetrated HA-PNIPAAm network as the hydrogel temperature crossed the cloud point led to a stiffening of the polymer network inside the hydrogel. LCST transition induces a heat mediated pulling of the IPN of HA-PNIPAAm structures causing the BDNHs to stiffen . The amplitude sweep was carried out from 0.1 to 500% strain at 37 °C to check the stability of the respective hydrogels with varying strain (Figure B).…”

“…LCST transition induces a heat mediated pulling of the IPN of HA-PNIPAAm structures causing the BDNHs to stiffen. 42 The amplitude sweep was carried out from 0.1 to 500% strain at 37 °C to check the stability of the respective hydrogels with varying strain (Figure 3B). The G′ values were higher than G″, indicating the viscoelastic nature of the hydrogels.…”

Topochemical polymerization in phenylalanine anchored chiral diacetylenes for chiroptical properties and tunable thermo-, halo-, solvatochromism

“…41 Such molecular recognition is of paramount importance in creating next-generation biocatalysts and biomaterials. [42][43][44][45] Phenylalanine motif with a p aromatic surface has recently emerged as an interesting yet simple amino acid building block to render a self-assembled network exhibiting interesting catalysis and piezoresponsive properties. [46][47][48] Herein, we exploit the chirality of the phenylalanine motif to design peptide-tethered diacetylene monomers, R,Ror S,S-DA-OMe, that could be topochemically photopolymerized to render interesting red-coloured fluorescent materials (Scheme 1).…”

Anion-responsive self-assembled hydrogels of a phenylalanine–TREN conjugate allow sequential release of propranolol and doxorubicin

“…4,12 The nanofibrillar self-assemblies of some PDAs can entrap solvent (or water) molecules to form supramolecular (hydro)gels that exhibit thermoreversibility, biocompatibility, biodegradability and tunability of nanostructures, which is needed in tissue engineering as well as in precision drug delivery applications. [13][14][15][16][17][18][19][20][21][22] Multiple noncovalent interactions such as hydrogen bonding, van der Waals inter-actions, π-π stacking, 23 hydrophobic interactions, 24 and even metal-coordination 25,26 are employed to stabilize these selfassemblies. Since these intermolecular interactions can be perturbed by different physical and chemical stimuli such as temperature, 27 light, [28][29][30] mechanical agitation, 31 pH, [32][33][34] solvent, 13 and ionic strength, [35][36][37][38] PDA self-assemblies can be designed to be responsive to these stimuli.…”