Near-Infrared Light-Controlled Dynamic Hydrogel for Modulating Mechanosensitive Ion Channels in 3-Dimensional Environment

The extracellular matrix (ECM) creates a dynamic mechanical environment for cellular functions, continuously influencing cellular activities via the mechanotransduction pathway. Mechanosensitive ion channels, recently identified as key mechanotransducers, convert mechanical stimuli into electrical or chemical signals when they detect membrane deformation. This process facilitates extracellular Ca²⁺ influx, cytoskeletal reorganization, and transcriptional regulation, all of which are essential for cellular physiological functions. In this study, we developed a fibrous hydrogel composite (PIC/OEG-NPs) with near-infrared (NIR) light-controlled dynamic mechanical properties to modulate mechanosensitive ion channels in cells, by using oligo-ethylene glycol (OEG)-assembled polyisocyanide (PIC) polymer and OEG-grafted conjugated polymer nanoparticles (OEG-NPs). PIC and OEG-NPs assemble into PIC/OEG-NPs composites through OEG-mediated hydrophobic interactions when heated. Under NIR stimulation, the PIC/OEG-NPs composites exhibit increased mechanical tension and form tighter fibrous networks due to their thermoresponsive behavior. These changes are reversible and allow for the dynamic regulation of mechanosensitive ion channels, including Piezo1 in transfected HEK-293T cells and the endogenous TRPV4 in human umbilical vein endothelial cells (HUVECs), by switching NIR on and off. Furthermore, this process enhances the angiogenic potential of HUVECs. In summary, we present a simple and effective platform for in situ modulation of mechanosensitive ion channels in 3 dimensions.