Towards the design of a conformational switchable zinc finger analogue regulating cellular behaviors.

Abstract

Dynamic conformational changes in the secondary structures of proteins are essential to their functions and can regulate diverse cellular events. Herein, along with our experimental collaborators, we report the design of a synthetic polymer-based secondary structure analogue of Zinc finger (ZnF). Acting as a conformational switch between unfolded and folded states triggered by the addition of Zn2+ and EDTA, ZnF enables the manipulation of the accessibility of conjugated cell adhesive ligands to cell membrane receptors, by hiding or exposing the cell adhesive ligands to the transmembrane protein receptors. On the basis of the self-avoiding walk (SAW) model, we investigated the distribution of end-to-end distance of the polymer chain of ZnF and estimated the free energy barrier that the zinc coordination motif had to overcome, thereby, predicting the feasible length of the polymer chains. Our work provided valuable guidance to experimental research on the synthesis of biomimetic dynamic secondary structures to precisely control cell-biomaterial interactions and mediate the desired cellular behaviors.