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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, αIIbβ3 and αVβ3. These integrins, expressed in circulating platelets vs. solid tissues, respectively, share the β3 subunit, bind similar ligands and have similar bent and extended conformations. Here, we report that in cells expressing equivalent levels of each integrin, αIIbβ3 mediates spreading on softer substrates than αVβ3. These effects correlate with differences in structural dynamics of the two integrins under force. All-atom simulations show that αIIbβ3 is more flexible than αVβ3 due to correlated residue motions within the α subunit domains. Single molecule measurements confirm that αIIbβ3 extends faster than αVβ3. These results reveal a fundamental relationship between protein function and structural dynamics in cell mechanosensing. 

Abstract Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate that different receptor–ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin α_IIbβ₃mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying drug-disease interactions and inter-individual variability, our work reveals a need for personalized anti-thrombotic drug selection that accommodates each patient’s pathological profile. 

Connected and automated vehicles (CAVs) offer many potential advantages, including improved traffic flow, reduction of traffic accidents, and increased freedom for adolescents and adults with restricted mobility. However, successful implementation of CAVs depends on several factors, especially acceptance and preferences by people. Specifically, during the earlier stage of deployment, CAVs will have to share the roads with human-driven vehicles (HDVs), which requires communication between CAVs and HDVs regarding their intentions and future actions. Therefore, as a first step in our research program, we conducted a survey of 182 U.S. drivers to assess their knowledge of CAVs and their thoughts about implementation. We report the survey results, accompanied by our interpretations.