Speaker
Description
Integrin activation dynamically orchestrates adhesion formation and cell motility within the heterogeneous extracellular space. However, mechanosensitive regulation of integrin β6 remains poorly understood. Using a traction‑free RGD membrane, integrin β6 colocalizes and nucleates micrometer‑scale clusters of viscous RGD ligands by 15 minutes and subsequently dissipates by 60 minutes. Swapping the cytoplasmic tail of integrin β6 with that of integrin β1 blocks the dissipation and confers persistent clustering, implicating the role of inside‑out signaling in maintaining adhesion stablization. We identify that kindlin2 as a key adaptor that binds weakly to integrin β6, compared to integrin β1. Supplementing additional kindlin2 or recruiting it via phosphatidylinositol 4-phosphate 5-kinase PIPK1 restores the clustering of integrin β6. Dissipated integrin β6 adopts a non‑active conformation, whereas strengthening the kindlin2-integrin β6 interaction stabilizes the active conformation and is required for integrin β6-mediated cell migration on soft PDMS. Taken together, these results demonstrate that kindlin‑dependent inside‑out activation of integrin β6 orchestrates mechanosensitive adhesion assembly and migration across compliant substrates.
