Abstract

Cardiovascular disease (CVD) accounted for 17.9 million deaths in 2019, with fibrosis contributing to nearly a quarter of these fatalities [1,2]. Fibrosis, characterized by excessive connective tissue formation, has been strongly linked to T cells, essential components of the immune system. This study explores the mechanisms of T cell activation and the subsequent changes in biophysical properties like diameter, stiffness, and elasticity, aiming to develop therapeutic strategies for fibrosis-related diseases, including CVD. Utilizing the micropipette aspiration technique, we accurately assessed T cell stiffness and observed a change in bulk cell stiffness upon activation. The results demonstrated increased fluid-like behavior in the activated T cells (Th17, Treg) during the elastic test, in contrast to the more solid-like characteristics exhibited by these cells after activation in the viscoelastic test, compared to that of a naive T cell (Th0). Our findings also suggest complex behaviors in T cells, where stiffness may vary depending on the rate at which pressure is applied. This observation opens new avenues for a series of future tests to explore this area in depth. Understanding these dynamics could have far- reaching implications for immunotherapy advancement, offering novel insights into how T cells respond to different mechanical stimuli and how the biophysical properties of the T cell are altered by activation and polarization. By tailoring therapeutic interventions to these unique cellular responses, we may enhance the efficacy of treatments for fibrosis-associated diseases. In conclusion, this study not only sheds light on the fundamental properties of T cells but also paves the way for targeted treatments and innovative research approaches. The potential to leverage these insights for improving patient outcomes in fibrosis-associated CVD represents a promising frontier in biomedical science.

Committee Chair

Matthew Bersi

Committee Members

Guy Genin Amit Pathak

Degree

Master of Science (MS)

Author's Department

Mechanical Engineering & Materials Science

Author's School

McKelvey School of Engineering

Document Type

Thesis

Date of Award

Summer 8-29-2023

Language

English (en)

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