Computational Modeling Predicts Novel Collagen Conformations During Mechanical Loading

Abstract

Collagens contribute to the mechanical strength of many tissues throughout the body and are generally resistant to ezymatic degradation. As structural proteins, collagens often experience in vivo mechanical forces such as expansion and contraction of blood vessels and tension on tendons and ligaments. Collagen crosslinking, which enhances the strength of these structural networks, occurs during tissue development and aging. While much is known about the structure of collagen, there is a paucity of data describing how mechanical force transmitted across these crosslinks affects molecular conformation. We hypothesized that mechanical force applied perpendicular to the long axis of the collagen triple helix will result in bending and microunfolding of the triple helix structure. To test this we used Steered Molecular Dynamics to model the conformation of a collagen peptide when subjected to perpendicular forces. In silico loading predicted that the collagen peptide had minimal resistance to bending, and exhibited increased curvature with no distinct disruption of the characteristic triple helix at low forces. As force increased, we observed that the helix began to fail and underwent a microunfolding event, where a loop pulled out from the complex. This local triple helix disruption was predicted to occur below covalent bond failure strength, suggesting that alternative molecular conformations occur within the molecule as structures are loaded before the onset of structural failure. We speculate that these changes may represent nano-damage to the structure and be a mechanism for energy storage and dissipation. Furthermore, these predicted conformational changes would precede macroscopic damage mechanisms.