Remote Control of Time-Regulated Stretching of Ligand-Presenting Nanocoils In Situ Regulates the Cyclic Adhesion and Differentiation of Stem Cells

Abstract

Native extracellular matrix (ECM) can exhibit cyclic nanoscale stretching and shrinking of ligands to regulate complex cell-material interactions. Designing materials that allow cyclic control of changes in intrinsic ligand-presenting nanostructures in situ can emulate ECM dynamicity to regulate cellular adhesion. Unprecedented remote control of rapid, cyclic, and mechanical stretching ("ON") and shrinking ("OFF") of cell-adhesive RGD ligand-presenting magnetic nanocoils on a material surface in five repeated cycles are reported, thereby independently increasing and decreasing ligand pitch in nanocoils, respectively, without modulating ligand-presenting surface area per nanocoil. It is demonstrated that cyclic switching "ON" (ligand nanostretching) facilitates time-regulated integrin ligation, focal adhesion, spreading, YAP/TAZ mechanosensing, and differentiation of viable stem cells, both in vitro and in vivo. Fluorescence resonance energy transfer (FRET) imaging reveals magnetic switching "ON" (stretching) and "OFF" (shrinking) of the nanocoils inside animals. Versatile tuning of physical dimensions and elements of nanocoils by regulating electrodeposition conditions is also demonstrated. The study sheds novel insight into designing materials with connected ligand nanostructures that exhibit nanocoil-specific nano-spaced declustering, which is ineffective in nanowires, to facilitate cell adhesion. This unprecedented, independent, remote, and cytocompatible control of ligand nanopitch is promising for regulating the mechanosensing-mediated differentiation of stem cells in vivo.