Immunoregulation of Macrophages by Controlling Winding and Unwinding of Nanohelical Ligands

Abstract

Developing materials with the capability of changing their innate features can help to unravel direct interactions between cells and ligand-displaying features. This study demonstrates the grafting of magnetic nanohelices displaying cell-adhesive Arg-Gly-Asp (RGD) ligand partly to a material surface. These enable nanoscale control of rapid winding ("W") and unwinding ("UW") of their nongrafted portion, such as directional changes in nanohelix unwinding (lower, middle, and upper directions) by changing the position of a permanent magnet while keeping the ligand-conjugated nanohelix surface area constant. The unwinding ("UW") setting cytocompatibility facilitates direct integrin recruitment onto the ligand-conjugated nanohelix to mediate the development of paxillin adhesion assemblies of macrophages that stimulate M2 polarization using glass and silicon substrates for in vitro and in vivo settings, respectively, at a single cell level. Real time and in vivo imaging are demonstrated that nanohelices exhibit reversible unwinding, winding, and unwinding settings, which modulate time-resolved adhesion and polarization of macrophages. It is envisaged that this remote, reversible, and cytocompatible control can help to elucidate molecular-level cell-material interactions that modulate regenerative/anti-inflammatory immune responses to implants.