Seminars

2012-11-13

Platelet Mechanobiology: Nanoscale Force Measurements and Microfluidic Shear Gradients using Soft Lithography Approaches

Asst. Prof. Nathan J. Sniadecki, University of Washington - Mechanical Engineering
Speaker's Website
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Platelets are the smallest cells in your blood, but they play a large role in its coagulation. They aggregate at a wound site in an injured vessel and form a hemostatic plug that prevents blood loss. The mechanobiology of platelets is very important to coagulation: internal forces generated by actin and myosin proteins can increase the adhesion strength of a platelet to a surface, while external forces from blood flow can activate platelets and initiate a hemostatic plug. These forces are nanoscale, so conventional assays are unable to study their effects on platelets. For this reason, my lab has developed soft lithography approaches to study the mechanics of platelets. We use arrays of vertical, flexible posts made from polydimethylsiloxane (PDMS) to measure the actin-myosin generated forces of platelets. Each post acts like a cantilever spring, so its deflection can be used to measure the actin-myosin force of a platelet. A single platelet is between 2 to 4 micrometers in diameter, so the PDMS posts we use need to be nanoscale in dimension and closely packed together for subcellular spatial resolution. To understand the effect of shear forces acting on platelets, we use microfluidic approaches to generate shear gradients and monitor the development of a nascent hemostatic plug. In the development of our tools, we have encountered issues with soft lithography of PDMS at the nanoscale, which I will highlight. Overall, our approaches for platelet mechanobiology have helped us uncovering novel insights into what proteins mediate platelet forces and the mechanobiology of platelets.