Coarse-Grained Martini 3 Model for Collagen Fibrils.

Abstract

Collagen is a prevalent protein in the animalia kingdom, especially in mammals. It is abundant in all connective tissue such as bone or ligaments and thus it is subjected to substantial mechanical forces. Crosslinks play an essential role for the structural and mechanical integrity of collagen, determining its stiffness and rigidity. Until now, studies on collagen including crosslinks have either been confined to fully atomistic simulations, which are computationally intensive and restrict the accessible time and length scales, or to coarse-grained descriptions that do not resolve the force response on a residue-level and therefore do not consider the triple helical structure and the connectivity of crosslinks. To bridge this gap, we report the development and validation of a computational model based on the Martini 3 coarse-grained force field, in which we parametrized the fibrillar collagen structure including crosslinks. We validated the model, through extensive equilibrium and non-equilibrium molecular dynamics simulations, against experimental properties and all-atom simulations. Because the type and distribution of crosslinks vary with aging, we expect that this collagen model can be employed to provide insights into age-related changes in tissue mechanics and guide the development of biomimetic materials.