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.

Bionanoscale Recognition Underlies Cell Fate and Therapy

“…Vinculin contributes to cell adhesion and extension. [29] The vinculin fluorescence intensities on the MoS 2 films were much higher than those on the PDMS film, explaining the cell differentiation and cell adhesion on MoS 2 films (Figure 2k).…”

A Topologically Engineered Gold Island for Programmed In Vivo Stem Cell Manipulation

“…[57] In addition, MSCs on the FSA 35 R-Ce IV -coupled substrate showed signifcantly reduced FAs and nuclear translocation of TAZ mechanotransducer in the case of inhibition of mechanosensing-related signaling molecules such as actin polymerization, rho-associated protein kinase (ROCK), and myosin II (Figure S20a,b, S21a,b and S22a,b). [58][59][60] Taken together, the optimal topologically engineered ligands within nanoscale island FSA 35 R-Ce IV upregulates FA complex assembly and mechanotransduction signaling, which promotes spreading, proliferation, and differentiation of MSCs.…”

All-Optical Modulation of Single Defects in Nanodiamonds: Revealing Rotational and Translational Motions in Cell Traction Force Fields

“…It is well established that cells exert traction forces to the extracellular matrix through focal adhesions, most of which are located at the cell periphery. By coupling with adhesion growth, flow of actin filament, and mechanosensitive proteins, the tractions generated at the cell–substrate interface exhibit complicated dynamics. ,− Indeed, it is commonly believed that cells utilize such traction forces to probe (by deforming) their surroundings and then adapt their actions accordingly. , When such force is disrupted by cell lysis, the stored energy in the substrate will be released and the material will return to its original/undeformed configuration. To monitor such changes, we establish a procedure for extracting the possible rotation-translation motions (in-plane) of NDs as fiduciary markers (Figure a).…”