Effect of Alcoholic Cosolvents on the Stability of a Supramolecular Collagenous Structure against Thermal and Mechanical Denaturations.

Alcohols used as cosolvents with water are known to have a broad range of effects on the native triple helix structure of collagen, from its stabilization (e.g., by glycerol) to its denaturation or its fibrillar precipitation (e.g., by ethanol). We consider gelatin hydrogels as collagenous supramolecular structures and study their resistance to fracture─a localized, stress-induced denaturation process of the collagenous triple-helix cross-links─in an alcoholic environment. Scanning a series of six alcohols, we find that, independently of their contrasted effect on the thermal melting of collagen helices, all of them hinder crack growth. We show that the corresponding increase of fracture energy is attributable to the effect of alcohols on both the differential and direct free energies of solvation, i.e., on their trend to favor the denaturation of the collagenous triple helix or the precipitation of the gelatin network. We find that the latter effect is dominant, all the more that the surface tension of the alcohol is lower. We propose a rationale for this remarkable correlation in the limit of vanishing cosolvent concentrations based on a cavity-filling approach.