The Molecular Origin of Water-Mediated Collagen Contraction

Abstract

The mechanical toughness of bone and teeth relies on residual stresses generated during mineralisation, where the dehydration of collagen fibrils leads to contraction, putting the mineral phase under compression. While macroscopic stiffening of collagen upon drying is well-documented, the atomic-level structural rearrangements driving this phenomenon have remained elusive. By performing molecular dynamics simulations, we demonstrate that collagen contraction is not homogeneous but is driven by specific charged motifs. We identify a critical sequence-dependent rule for contraction: oppositely charged side chains must be separated by at least four residues to drive backbone contraction. While salt bridges can form between side chains at a distance less than four residues without perturbing the helix, those at greater distances cannot form without rupturing backbone hydrogen bonds. Consequently, dehydration forces these distant charges together, breaking local backbone structure and driving collagen contraction. These findings imply that collagen sequences are evolutionarily tuned to actively control tissue mechanics and redefines collagen as an active mechanical element rather than a passive scaffold. Furthermore, this framework provides a molecular basis for understanding mechanical failure associated with pathologies and ageing, while simultaneously opening avenues for designing bio-inspired materials with tunable pre-stress and fracture resistance.