Date of Graduation

5-2025

Document Type

Thesis

Degree Name

Bachelor of Science in Physics

Degree Level

Undergraduate

Department

Physics

Advisor/Mentor

Zhang, Jian

Committee Member

Shew, Woodrow

Second Committee Member

Shields, Deanna

Abstract

Physical forces drive many cellular processes such as migration and proliferation. A metastatic tumor will have invasive strands/chains that extend from the main tumor. These chains of cells collectively migrate away from the main tumor to establish new colonies elsewhere in the body. However, how physical forces drive this collective invasion and the required energy for this process is not well understood. Invasion of a metastatic tumor to surrounding tissues leads to a majority of cancer-associated death and is often a collective effort among cells, it is therefore important to fully understand the process behind collective cancer invasion.

The goal of this project is to determine the forces that drive collective cell migration in a one-dimensional system of cells. Analyzing a single strand of migrating cells allows for an in vitro analysis of metastatic chains developed by a tumor.

To confine migrating cells to a one-dimensional chain we engineered the extracellular environment via micropatterning such that cells only migrated along a thin line of extracellular matrix proteins patterned onto an elastic substrate. Once contained on a patterned elastic substrate with known physical properties, cell-matrix, and cell-cell forces were quantified via Traction Force Microscopy (TFM) by tracking substrate deformations. To connect these forces with cellular bioenergetics, we quantify the energy level of these migrating cell chains by measuring the cellular NADH:NAD+ ratio with a genetically encoded molecular probe.

Current results suggest that cells leading the collective migration experience greater forces, implying that these cells have greater bioenergetic needs. We have not found a statistically significant correlation between cellular energy and force generation, more replicates are needed to establish a relationship between the two.

Keywords

mechanobiology; collective migration; traction force microscopy; cancer cell migration

Download

Share

COinS