Hydration water drives elastin's entropic elasticity

Elastin endows arteries, skin and lungs with elasticity, yet the molecular origin of its entropic recoil remains debated. Using multi-microsecond all-atom simulations of a representative elastomeric region of human tropoelastin, the monomeric precursor of elastin, we quantify protein conformational entropy, hydration-water entropy, and protein- and water-mediated interaction enthalpies during stretching. Protein conformational entropy decreases modestly overall, with heterogeneous local entropic responses governed by secondary structure and sequence context. In contrast, hydration water provides the dominant unfavorable entropic contribution because stretching recruits many water molecules from bulk into a persistently low-entropy first hydration layer. Stretching also disrupts favorable intra-protein interactions while strengthening protein-water interactions, producing opposing enthalpic contributions that largely compensate the entropic penalty. Together, these results support a hydration-coupled thermodynamic mechanism in which water is the dominant entropic contributor to elastin recoil within a strongly compensating enthalpy-entropy balance.