How Hydration Weakens Collagen: A Mesoscale Energy Decomposition of Type I and Type II Fibrils.

This study presents a hydration-dependent mesoscale model to quantify intermolecular cohesive energy in Type II collagen fibrils, the primary structural component of articular cartilage. In contrast to the tightly packed, low-hydrated Type I fibrils, Type II molecules form a loosely organized network in a highly hydrated matrix. Building on Buehler's coarse-grained framework, we introduced hydration-sensitive corrections and quantified the major contributors to fibrillar cohesion: hydrogen bonding, van der Waals forces, water-mediated bridges, hydrophobic interactions, and coulombic attractions. Quantitatively, the total cohesive energy of Type II collagen was estimated at 2,208 kcal/mol per tropocollagen molecule, substantially lower than 3,046 kcal/mol in Type I collagen. Among the contributing factors, hydrophobic interactions dominated in Type II, accounting for ~52% of the total cohesive energy, followed by coulombic and hydrogen-bonding contributions, whereas van der Waals and water-mediated interactions were substantially weakened by hydration-induced spacing and dielectric screening. To our knowledge, these findings provide the first quantitative energy decomposition of Type II fibrils. They offer insights into the molecular determinants of cartilage flexibility, age-related stiffening, and matrix degradation in osteoarthritis and may help guide the development of biomimetic cartilage constructs.