Graduate student Yun Zhang wins poster prize
Chemistry graduate student Yun Zhang (Salaita Group) received an award for "Best Poster” at the 2015 Gordon Research Conference "Fibronectin, Integrins & Related Molecules.” The conference, a key scientific meeting for those interested in integrins and the interactions between cells with the extracellular matrix in development, homeostasis and disease, took place February 10th - 15th at the Ventura Beach Marriott, Ventura, California.
Zhang’s poster was presented as part of the session “"Mechanobiology and Matrix Dynamics.” The full abstract for the poster appears below:
Mapping integrin forces with high spatial and temporal resolution during platelet activation
Yun Zhang, Yongzhi Qui, Wilbur Lam, Khalid Salaita
Platelets play an essential role in hemostatic response by forming blood clots that seal the damaged vessel sites and promote vascular healing. Through the coordination of physical-chemical interaction between integrin aIIbb3, actin, and myosin, platelets adhere and generate forces to strengthen their adhesion to the exposed extracellular matrix and fibrin mesh. Recent work suggests that platelets sense the stiffness of their extracellular matrix and respond by tuning their activation levels. Nonetheless, a fundamental question pertaining to the role of mechanics in platelet activation is whether the aIIbb3 integrins experience mechanical tension during activation and its precise magnitude, and spatial and temporal distribution during platelet activation. To address this question, we first immobilized integrin ligands onto a supported lipid membrane and found that laterally mobility markedly dampens the activity of ligands for aIIbb3 integrins. Next, we developed DNA-based fluorescence tension probes to visualize piconewton scale forces during platelet activation cascades. These probes provided the highest resolution force maps associated with platelet activation to date. Interestingly, we found that platelets exert force through filopodia nearly instantaneously when activated by contact with the sensor surface. As filopodia coalesced to form circumferential lamellae, the tension was greatly increased and specifically accumulated at the cell periphery and the center of the cell area. The tension at the center of the platelet was highly influenced by myosin contractility. Finally, By comparing the tension signal associated with a small library of integrin ligands that bind aIIbb3, we found that platelet-generated forces are highly dependent on the chemical identify of the ligands. For example, cyclic RGD ligands experience over 19 pN of tension, whereas the HHLGGAKQAGD ligand experience values of tension greater than 2.4 pN but lower than 4.2 pN. Taken together, this data demonstrates that mechanical forces play a critical role in platelet activation and newly emerging molecular tension probes provide a power approach to elucidate the role of integrin tension in platelet activation. This may potentially guide new hemostatic or antithrombotic treatments.
