Directed Conformational Switching of a Zinc Finger Analogue Regulates the Mechanosensing and Differentiation of Stem Cells.

The dynamic conformational changes in the secondary structures of proteins are essential to their functions and can regulate diverse cellular events. Herein we report the design of a synthetic polymer-based secondary structure analogue of a zinc finger (ZnF) by introducing a zinc coordination motif to overcome the free energy barrier predicted by theoretical calculations and fold-free polymer chains. The conformational switching between unfolded and folded state of the ZnF analogue can be triggered in situ to drastically manipulate the accessibility of conjugated cell adhesive ligands to the cell membrane receptors, thereby effectively controlling the adhesion, spreading, mechanosensing, and differentiation of stem cells. We believe that emulating the dynamic secondary structures of proteins via rational design of a folded synthetic polymer-cation complex is a promising strategy for developing bioactive materials to mediate desired cellular functions.