The competition between surface adsorption and folding of fibril-forming polypeptides

TL;DR

This study uses a coarse-grained model to explore how surface interactions influence the folding and adsorption pathways of fibril-forming polypeptides, revealing temperature-dependent mechanisms and the impact of surface attraction strength.

Contribution

It uncovers the temperature-dependent folding pathways and the non-monotonic effect of surface attraction on polypeptide folding and adsorption, providing insights into fibril formation mechanisms.

Findings

Two folding pathways depend on temperature.

Surface attraction strength affects folding temperature.

Weakly attractive surfaces promote folding.

Abstract

Self-assembly of polypeptides into fibrillar structures can be initiated by planar surfaces that interact favorably with certain residues. Using a coarse grained model, we systematically studied the folding and adsorption behavior of a $\beta$-roll forming polypeptide. We find that there are two different folding pathways depending on the temperature: (i) at low temperature, the polypeptide folds in solution into a $\beta$-roll before adsorbing onto the attractive surface, (ii) at higher temperature, the polypeptide first adsorbs in a disordered state, and folds while on the surface. The folding temperature increases with increasing attraction, as the folded $\beta$-roll is stabilized by the surface. Surprisingly, further increasing the attraction lowers the folding temperature again, as strong attraction also stabilizes the adsorbed disordered state, which competes with folding of the polypeptide. Our results suggest that to enhance the folding, one should use a weakly attractive surface. They also explain the recent experimental observation of the non-monotonic effect of charge on the fibril formation on an oppositely charged surface [C. Charbonneau, et al., ACS Nano, 8, 2328 (2014)].