Controlling the Trimerization of the Collagen Triple-Helix by Solvent Switching.

Abstract

Collagen hybridizing peptides (CHPs) are a powerful tool for targeting collagen damage in pathological tissues due to their ability to specifically form a hybrid collagen triple-helix with the denatured collagen chains. However, CHPs have a strong tendency to self-trimerize, requiring preheating or complicated chemical modifications to dissociate their homotrimers into monomers, which hinders their applications. To control the self-assembly of CHP monomers, we evaluated the effects of 22 cosolvents on the triple-helix structure: unlike typical globular proteins, the CHP homotrimers (as well as the hybrid CHP-collagen triple helix) cannot be destabilized by the hydrophobic alcohols and detergents (e.g., SDS) but can be effectively dissociated by the cosolvents that dominate hydrogen bonds (e.g., urea, guanidinium salts, and hexafluoroisopropanol). Our study provided a reference for the solvent effects on natural collagen and a simple effective solvent-switch method, enabling CHP utilization in automated histopathology staining and in vivo imaging and targeting of collagen damage.