Conformational response of αβ and αβ integrins to force.

As major adhesion receptors, integrins transmit biochemical and mechanical signals across the plasma membrane. These functions are regulated by transitions between bent and extended conformations and modulated by force. To understand how force on integrins mediates cellular mechanosensing, we compared two highly homologous integrins, αβ and αβ. These integrins, expressed in circulating platelets vs. solid tissues, respectively, share the β subunit, bind similar ligands and have similar bent and extended conformations. Here, we report that in cells expressing equivalent levels of each integrin, αβ mediates spreading on softer substrates than αβ. These effects correlate with differences in structural dynamics of the two integrins under force. All-atom simulations show that αβ is more flexible than αβ due to correlated residue motions within the α subunit domains. Single molecule measurements confirm that αβ extends faster than αβ. These results reveal a fundamental relationship between protein function and structural dynamics in cell mechanosensing.