Date of Award

Summer 8-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Mechanical & Aerospace Engineering

Program/Concentration

Mechanical Engineering

Committee Director

Venkat Maruthamuthu

Committee Member

Taylor Sloey

Committee Member

Oleksandr Kravchenko

Abstract

Epithelial cells are among the most abundant cell types in the human body, making up sheets of epithelial tissues that cover the linings of organs and body cavities. Cellular adhesion and force transmission across epithelial tissues are crucial in maintaining tissue integrity and ensuring proper tissue regeneration. Defects in cellular force transmission have been found in various diseases, including cancer. Force transmission at cell-cell and cell-ECM junctions drive cell survival and development. It has been previously shown that changes in cell-ECM traction directly modulates forces at cell-cell contacts. In this study, we aim to determine the effects of perturbations in intercellular forces on traction forces. Traction force microscopy and the traction force imbalance method were used to calculate the forces at cell-cell and cell-ECM contacts. We also utilized vinculin, a protein known to regulate force transmission at these junctions. We confirm previous results showing that in the absence of vinculin, traction forces and intercellular forces are decreased. In addition, we show that when vinculin is rescued, both traction and intercellular forces return to normal levels. In order to modulate intercellular forces, we consider a mixed cell pair with a vinculin rescue cell and a vinculin knockout cell. Results show that even with one cell (vinculin rescue) having the ability to exert normal levels of traction forces, when paired with a cell lacking this ability (vinculin knockout), the vinculin rescue cell modulates its traction forces to lower levels. These results suggest that changes in intercellular forces at the cell-cell contact modulate traction forces at the cell-ECM contact. Understanding the mechanical relationship between cell-cell and cell-ECM junctions provides a more robust understanding of force transmission across epithelial tissues and has implications for understanding defects in force transmission in disease states like cancer and fibrosis as well.

Rights

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/ This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).

DOI

10.25777/xeff-gf20

ISBN

9798293842308

ORCID

0000-0002-6565-1125

Download

Share

COinS