Modulation of Macrophages by In Situ Ligand Bridging

Abstract

Extracellular matrix (ECM) proteins containing cell-attachable Arg-Gly-Asp (RGD) sequences exhibit variable bridging and non-bridging in fibronectin-collagen and laminin-collagen complexes that can regulate inflammation, tissue repair, and wound healing. In this study, linking molecule-mediated conjugation of 1D magnetic nanocylinders (MNCs) to material surfaces pre-decorated with gold nanospheres (GNSs) is performed, thereby yielding RGD-coated MNCs (RGD-MNCs) over RGD-coated GNSs (RGD-GNSs) in a non-bridging state. The RGD-MNCs are drawn closer to the RGD-GNSs via magnetic field-mediated compression of the linking molecules to establish the bridging between them. Relative proportion of the RGD-MNCs to the RGD-GNSs is optimized to yield effective remote stimulation of integrin binding to variably bridged RGDs similar to that of invariably bridged RGDs used as a control group. Remote manipulation of the RGD bridging facilitates the attachment structure assembly of macrophages that leads to pro-healing/anti-inflammatory phenotype acquisition. In contrast, the non-bridged RGDs inhibited macrophage attachment that acquired pro-inflammatory phenotypes. The use of various nanomaterials in constructing heterogeneous RGD-coated materials can further offer various modes in remote switching of RGD bridging and non-bridging to understand dynamic integrin-mediated modulation of macrophages that regulate immunomodulatory responses, such as foreign body responses, tissue repair, and wound healing.