Non-equilibrium remodelling of collagen-IV networks in silico

Collagen-IV is one of the main component 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 coarse grained models for collagen-IV molecules that retain biochemical bond specificity and coarse-grain at two 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 continually turns over, with rates that are linked with enzyme activity and that affect tissue organisation. We then explore the effects of equilibrium versus out-of-equilibrium (enzymatic) bond remodelling. We find that the latter 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.