PhysBio Seminar: Alexander Bershadsky

Note the unusual place: Amphi de l’Institut Curie, bâtiment 111

Integrin mediated cell-matrix adhesions and their regulation by microtubules

We discuss here two major types of cell-matrix adhesions mediated by transmembrane receptors of integrin family – focal adhesions, formed by cells on locally flat surfaces coated with extracellular matrix proteins (integrin ligands), and fibrillar adhesions, associated with cell-derived fibrils containing protein fibronectin. Focal adhesions are linked with actin filament bundles and probing the matrix stiffness by transmitting and sensing forces. Activation/inactivation of myosin-II contractility trigger assembly/disassembly of focal adhesions, respectively. Unlike focal adhesions, fibrillar adhesions associate with sparse actin network and do not disassemble upon myosin-II inhibition. Moreover, specific nano-topographical cues – nanofibers or nanogrooves – trigger formation of fibrillar adhesions in a myosin-II-independent fashion, while excessive activation of myosin II, or increase of membrane tension, trigger the disassembly of fibrillar adhesions. Theoretical modelling and
 experimental data suggest that formation of fibrillar adhesions along nano-topographical cues can be explained by a special shape of adhesion receptors, preferably connecting the cell and substrate surfaces tilted relatively to each other. The shape of α5β1 integrin, the only one found in fibrillar adhesions, satisfies to this condition. Microtubules are targeted to focal and fibrillar adhesions via KANK family proteins. Using genetic depletion and optogenetic tools, we deciphered mechanism of microtubule-driven adhesion regulation. Disconnecting microtubules from integrin adhesions triggers the release of microtubule-associated Rho activator GEF-H1, subsequent activation of Rho and assembly of myosin II filaments, which then remodel the focal and fibrillar adhesions in a differential manner, as described above. Thus, microtubules function as signaling structures locally regulating myosin II contractility in response to their interactions with integrin adhesions.

Further reading:
Rafiq NBM, … Bershadsky AD. A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions. Nat Mater. 2019;18(6):638-649.
Aureille J, … Bershadsky AD. Focal adhesions are controlled by microtubules through local contractility regulation. EMBO J. 2024; 43(13):2715-2732.
Farrugia AJ … Bershadsky AD. Fibrillar adhesions are the primary integrin complexes shaped by matrix topography. bioRxiv 2025; 2025.11.26.690075.