fig14

Figure 14. Schematic diagram of the direct mechano-regulation mechanism underlying nanotopographic structure-mediated immune responses. Nanotopographic structures modulate traction force, membrane tension, and contact pressure on the immune cell membrane. Traction force and contact pressure affect the configuration of integrins, recruiting talin to their cytoplasmic tails, thereby regulating cytoskeletal activation. Changes in integrin-mediated cytoskeletal function influence the nuclear translocation of the mechanotransduction molecules YAP/TAZ and MRTF-A, thus regulating the gene expression of inflammatory factors. Alternation of the activity of integrins also affects cell focal adhesion activity, as well as downstream PI3K-Akt signaling and subsequent NF-κB signaling. Additionally, activation of LFA-1 promotes B-cell and T-cell activations. Membrane tension can activate Piezo1, TRPV, and Caveolae. Force-induced opening of TRPV4 and Piezo1 results in Ca²⁺ influx, promoting activation of NF-κB and synthesis of EDN1, which facilitates the accumulation of HIF-1α. NF-κB and HIF-1α translocate to the nucleus, driving the expression of inflammatory genes. Additionally, Piezo1-mediated Ca²⁺ influx can activate TCR and BCR. Membrane tension also leads to the disassembly of caveolae, releasing co-localized, inflammation-related signaling molecules such as TLR4, which activate downstream NF-κB signaling pathways. Additionally, caveolae control the distribution of BCR nanoclusters.