Conformational response of α(IIb)β(3) and α(V)β(3) 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, α(IIb)β(3) and α(V)β(3). These integrins, expressed in circulating platelets vs. solid tissues, respectively, share the β(3) subunit, bind similar ligands and have similar bent and extended conformations. Here, we report that in cells expressing equivalent levels of each integrin, α(IIb)β(3) mediates spreading on softer substrates than α(V)β(3). These effects correlate with differences in structural dynamics of the two integrins under force. All-atom simulations show that α(IIb)β(3) is more flexible than α(V)β(3) due to correlated residue motions within the α subunit domains. Single molecule measurements confirm that α(IIb)β(3) extends faster than α(V)β(3). These results reveal a fundamental relationship between protein function and structural dynamics in cell mechanosensing.