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Publication Date

Summer 2024

Degree Type

Thesis - Campus Access Only

Degree Name

Master of Science (MS)

Department

Chemical and Materials Engineering

Advisor

Anand Ramasubramanian; Sang-Joon Lee; Folarin Erogbogbo; Kinjal Dabiswas

Abstract

The formation of blood clots, also known as the coagulation cascade, is driven by cascading enzymatic interactions that stop blood from leaving vessels at sites of injury while maintaining hemostasis. The platelets and fibrin present within a blood clot can be affected by mechanical and biochemical interactions that may influence overall clot strength and stiffness. A portion of these interactions includes the cross-linking of fibrin fibers by Factor XIII-A, whose activity increases the clot resistance to lysis. Additionally, the distribution of receptors upon platelet surfaces is critical to understand how platelets up and downregulate specific functions between their activated state. To investigate platelet-fibrin interactions mediated through FXIII-A presented on activated platelet surfaces, we utilized confocal microscopy and image analysis to investigate differences between platelet suspensions treated with T101, to inhibit FXIII, and the addition of extracellular FXIII-A to mimic natural physiological conditions. Additionally, the use of novel super resolution expansion microscopy was established as a method of investigating platelet receptor distributions, namely GP Ib whose function leads to platelet adhesion. Imaging revealed that the inhibition of FXIII reduces the likelihood of platelet-fibrin interactions. Analysis of individual expanded resting and activated platelets revealed that GP Ib redistributes across the platelet membrane and can exist in various patterns in activated platelets. These results indicate that FXIII is important for platelet mechano-sensing and optimized protocol for visualization of receptor distribution upon the platelet surface at the nanoscale.

Available for download on Tuesday, November 13, 2029

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