Soft Polymeric Matrix as a Macroscopic Cage for Magnetically Modulating Reversible Nanoscale Ligand Presentation

A physical, noninvasive, and reversible means of controlling the nanoscale presentation of bioactive ligands is highly desirable for regulating and investigating the time-dependent responses of cells, including stem cells. Herein we report a magnetically actuated dynamic cell culture platform consisting of a soft hydrogel substrate conjugated with RGD-bearing magnetic nanoparticle (RGD-MNP). The downward/upward magnetic attraction conceals/promotes the presentation of the RGD-MNP in/on the soft hydrogel matrix, thereby inhibiting/enhancing the cell adhesion and mechanosensing-dependent differentiation. Meanwhile, the lateral magnetic attraction promotes the unidirectional migration of cells in the opposite direction on the hydrogel. Furthermore, cyclic switching between the "Exposed" and "Hidden" conditions induces the repeated cycles of differentiation/dedifferentiation of hMSCs which significantly enhances the differentiation potential of hMSCs. Our design approach capitalizes on the bulk biomaterial matrix as the macroscopic caging structure to enable dynamic regulation of cell-matrix interactions reversibly, which is hard to achieve by using conventional cell culture systems.