Date of Award

8-31-2026

Document Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department

Physics, Applied

First Advisor

Professor Jonathan Celli

Abstract

Oral squamous cell carcinoma (OSCC) invasion is strongly regulated by interactions between tumor cells and the surrounding extracellular matrix (ECM). However, localized ECM mechanical changes during tumor invasion and after photodynamic therapy (PDT) remain insufficiently understood. This study mainly investigated: time-dependent viscoelastic remodeling of collagen-I ECM during TR146 tumor cell invasion, visualization of time-dependent TR146 tumor cell invasion and post-PDT response using live/dead fluorescence imaging, and the direct effect of PpIX-mediated PDT on the viscoelastic properties of spheroid-free collagen-I ECM. Three-dimensional TR146 spheroids were generated using a non-adherent agarose-based method, surrounded by a basement-membrane-like Matrigel layer, and embedded in 3.0 mg/mL collagen-I ECM. Passive particle-tracking microrheology was used to determine the frequency-dependent storage modulus  and loss modulus  in ECM regions near and far from the spheroid during invasion over time. Separate spheroid-free collagen-I samples containing 10, 20, and 30 μM PpIX were used to distinguish direct PDT-induced mechanical changes in collagen-I ECM from tumor-mediated ECM remodeling. During invasion, both  and  progressively decreased in near-field ECM regions relative to far-field ECM regions, indicating localized and time-dependent ECM softening, likely caused by proteolytic degradation and force-mediated collagen remodeling. Live/dead imaging showed progressive outward migration of peripheral viable tumor cells. Following ALA-mediated PDT, dead-cell fluorescence became dominant throughout the spheroid and invaded regions, confirming extensive treatment-induced cytotoxicity. In spheroid-free collagen-I ECM, increasing PpIX concentration progressively reduced both  and  after PDT, suggesting direct oxidative weakening of the collagen network. Overall, these findings demonstrate that TR146 tumor invasion progressively softens the local collagen microenvironment, that TR146 tumor invasion occurs via the proliferation and movement of peripheral viable cells, and that PpIX-mediated PDT can affect both invasive tumor cells and the mechanical integrity of the surrounding collagen ECM.

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Additional Files

Himantha's Signature Page-1.pdf (203 kB)

Thesis Final Version NEW 2 (Himantha) .pdf (1924 kB)

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