Temperature-favoured assembly of collagen is driven by hydrophilic not hydrophobic interactions.

It has become almost axiomatic that protein folding and assembly are dominated by the hydrophobic effect. The contributions from this, and other, hydrophilic interactions can now be better distinguished by direct measurement of forces between proteins. Here we report the measurement of forces between triple helices of type I collagen at different temperatures, pH and solute concentrations. We separate repulsive and attractive components of the net force and analyze the origin of the attraction responsible for the collagen self-assembly. In this case the role of the hydrophobic effect appears to be negligible. Instead, water-mediated hydrogen bonding between polar residues is the most consistent explanation.