Non-equilibrium remodelling of collagen-IV networks in silico

Abstract

Collagen IV is one of the main components of the basement membrane, a layer of material that lines the majority of tissues in multicellular organisms. Collagen-IV molecules assemble into networks, providing stiffness and elasticity to tissues and informing cell and organ shape, especially during development. In this work, we develop two coarse grained models for collagen-IV molecules that retain biochemical bond specificity and coarse-grain at different length scales. Through molecular dynamics simulations, we test the assembly and mechanics of the resulting networks and measure their response to strain in terms of stress, microscopic alignment, and bond dynamics. Within the basement membrane, collagen-IV networks rearrange by molecule turnover, which affects tissue organisation and can be linked with enzyme activity. Here we explore network rearrangements via bond remodelling -- the process of dynamical breaking and remaking of bonds between network molecules. We then investigate the effects of active (enzymatic) bond remodelling. We find that this non-equilibrium remodelling allows a network to keep its integrity under strain, while relaxing fully over a variety of timescales - a dynamic response that is unavailable to networks undergoing equilibrium remodelling.