Sarthak Gupta

Date of Award

9-15-2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physics

Advisor(s)

Jennifer Schwarz

Second Advisor

Alison Patteson

Keywords

Cell motility;Chromatin;Coronavirus;Living Systems;Nucleus;Tissue

Subject Categories

Physical Sciences and Mathematics | Physics

Abstract

Living systems are constrained by the principles of physics. This thesis investigates the physical principles underlying four different problems from living systems, spanning several lengthscales and timescales. I begin by investigating how cell surface filaments influence the virus entry process into a cell. By considering physical parameters such as filament density, stretching, and bending rigidities, the study reveals that these coreceptors can either assist or hinder viral uptake through crumpling or folding around the virus. Next, I explore the underlying mechanism of abnormal nuclear shapes, including bulge and wrinkle formations. These are found to be influenced by chromatin transcriptional activity and inter and intra-chromatin links. Specifically, bulge formations are shown to be driven by chromatin-correlated motion and are dependent on motor and chromatin interconnectedness. Moving outwards, I examine the role of the cell’s internal components in confined cell motility and polarity. By focusing on the rigidity of the cytoskeleton and nucleus, I showed the difference in cell speeds and polarity behavior in confinement, as demonstrated in microchannel experiments using vimentin-null and wild-type cells. Finally, I investigated tissue behavior under compression for both solid and fluid-like tissues. By comparing cell shape, I reveal that solid-like tissues exhibit more frustration due to their limited ability to change neighbors, while fluid-like tissues show more dynamic behavior. In all cases, incorporating ideas from physics, such as mechanical forces, activity, and geometry, results in a deeper understanding of living systems’ workings. In the process, new physical phenomena are also discovered, contributing to our knowledge of the intricate workings of living systems.

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Open Access

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