Mechanical Unfolding\nof Network Nodes Drives the Stress\nResponse of Protein-Based Materials

Biomaterials synthesized from cross-linked folded proteins\nhave\nuntapped potential for biocompatible, resilient, and responsive implementations,\nbut face challenges due to costly molecular refinement and limited\nunderstanding of their mechanical response. Under a stress vector,\nthese materials combine the gel-like response of cross-linked networks\nwith the mechanical unfolding and extension of proteins from well-defined\n3D structures to unstructured polypeptides. Yet the nanoscale dynamics\ngoverning their viscoelastic response remains poorly understood. This\nlack of understanding is further exacerbated by the fact that the\nmechanical stability of protein domains depends not only on their\nstructure, but also on the direction of the force vector. To this\nend, here we propose a coarse-grained network model based on the physical\ncharacteristics of polyproteins and combine it with the mechanical\nunfolding response of protein domains, obtained from single molecule\nmeasurements and steered molecular dynamics simulations, to explain\nthe macroscopic response of protein-based materials to a stress vector.\nWe find that domains are about 10-fold more stable when force is applied\nalong their end-to-end coordinate than along the other tethering geometries\nthat are possible inside the biomaterial. As such, the macroscopic\nresponse of protein-based materials is mainly driven by the unfolding\nof the node-domains and rearrangement of these nodes inside the material.\nThe predictions from our models are then confirmed experimentally\nusing force-clamp rheometry. This model is a critical step toward\ndeveloping protein-based materials with predictable response and that\ncan enable applications for shape memory and energy storage and dissipation.