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Publication Date

Summer 2021

Degree Type

Thesis - Campus Access Only

Degree Name

Master of Science (MS)

Department

Biomedical Engineering

Advisor

Anand K. Ramasubramanian

Subject Areas

Biomedical engineering; Biomechanics

Abstract

Blood clots are essential in the stopping of bleeding but they can also be lethal when they create unwanted obstruction in the vessels. This makes it important to investigate the mechanical properties of blood clots. Fibrin and platelets have their own unique contribution to the properties of the blood clots but it is the interactions between platelets and fibrin that is critical in the evolution of clot properties. To understand these interactions we studied the effect of fibrin-bound platelets on mechanical and structural properties of the clot. We used a custom designed forcemeasurement system to obtain the response of the blood clots under uniaxial strain, and the interaction between platelets and fibrin using fluorescence microscopy and image analysis. We used blebbistatin, ML7, Y27632, eptifibatide and T101 to inhibit non-muscle myosin IIa, GP IIb/IIIa, and fibrin crosslinking. The mechanical measurements revealed that these treatments significantly reduced the stiffness of the clots. The image analysis results showed that the inhibitors signficantly decreased the size of the platelet aggregates and platelet-fibrin interactions. Further analysis demonstrated that the tensile modulus of the clots correlated linearly with platelet-bound fibrin estimated from image analysis. These results indicate that fibrin bound to platelets is a critical determinant of clot stiffness.

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