Platelets are key players in both hemostasis and thrombosis. Mechanical stimuli are important in the circulation system. We strive to understand platelet activation, mechanotransduction, and hyperreactivity by characterizing surface receptor-ligand binding kinetics and intracellular signaling using tools such as the biomembrane force probe, biosensors, and mutation studies.
In hemostasis, platelets adhere and aggregate on the site of vascular injury. Under high hemodynamic flows commonly found in arteries, the early-stage platelet adhesion is mediated by two receptor-ligand pairs: 1) Platelet translocation by binding of glycoprotein (GP) Ibα to the A1 domain of von Willebrand factor (VWF), a multimeric plasma glycoprotein immobilized on the subendothelium; 2) Platelet firm adhesion by binding of activated integrin αIIbβ3 to AGDV and RGD domains of matrix immobilized fibrinogen and VWF, respectively. These binding events activate the platelets through mechanotransduction. Platelets can become hyperreactive in abnormal conditions such as diabetes, obesity, and hypertension, leading to thrombosis. Our research targets on the mechanical adhesion and activation of platelets. We aim to answer two main questions: 1) How are the mechanical signals transmitted through the surface receptors and translated to biochemical signals inside the platelet; 2) How are platelet adhesiveness and activity dysregulated in various disease states. We incorporate our unique single-cell force probe with other cutting edge techniques, e.g., the FRET biosensor and calcium imaging, to link mechanical stimuli with downstream signaling events such as calcium flux and upregulation of cGMP.