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

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 heat-stiffening 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 non-equilibrium self-assembled peptide fiber toward non-linear biomechanics analogous to the actinomyosin network ubiquitous in cells and tissues.