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

Abstract

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.

Histone Modification of Osteogenesis Related Genes Triggered by Substrate Topography Promotes Human Mesenchymal Stem Cell Differentiation

“…The process of mechanotransduction and differentiation of stem cells is highly dependent on the cell adhesion to the substrate. , Our previous study has demonstrated that the microstructure on the hPC surface enhanced the expression of total integrin α2, activation of integrin α3, and secretion of the ECM component Laminin-5 in hBMSCs, in comparison to sPC and mPC substrates . In this study, we further examined the focal adhesion complex, integrin β1 subunit activation, and FAK phosphorylation, all of which play a major role in promoting MSC osteogenic differentiation and osteoblast maturation. − We observed that hBMSCs exhibited a greater number of focal adhesions on hPC substrate, as evidenced by vinculin staining (Figure A).…”