<i>In Situ</i> Magnetic Control of Macroscale Nanoligand Density Regulates the Adhesion and Differentiation of Stem Cells

Abstract

Developing materials with remote controllability of macroscale ligand presentation can mimic extracellular matrix (ECM) remodeling to regulate cellular adhesion <i>in vivo</i>. Herein, we designed charged mobile nanoligands with superparamagnetic nanomaterials amine-functionalized and conjugated with polyethylene glycol linker and negatively charged RGD ligand. We coupled negatively a charged nanoligand to a positively charged substrate by optimizing electrostatic interactions to allow reversible planar movement. We demonstrate the imaging of both macroscale and <i>in situ</i> nanoscale nanoligand movement by magnetically attracting charged nanoligand to manipulate macroscale ligand density. We show that <i>in situ</i> magnetic control of attracting charged nanoligand facilitates stem cell adhesion, both <i>in vitro</i> and <i>in vivo</i>, with reversible control. Furthermore, we unravel that <i>in situ</i> magnetic attraction of charged nanoligand stimulates mechanosensing-mediated differentiation of stem cells. This remote controllability of ECM-mimicking reversible ligand variations is promising for regulating diverse reparative cellular processes <i>in vivo</i>.