Measurements of the solubility of calf-skin tropocollagen in neutral phosphate buffers in the temperature range 20–37°C show that native collagen fibril formation is an endothermic process made thermodynamically favourable by a large positive entropy of precipitation associated with structural changes in the surrounding solvent. The effect of inorganic ions and small solute molecules on precipitation seems to be correlated with their structural effects on liquid water. Heterogeneity in the precipitation properties of the collagen solutions may be related to changes in the configurational entropy of the macromolecules due to intramolecular cross-linking.
