Sneha Sundaramoorthy
BME MS Thesis Defense Presentation
Date: 2026-04-01
Time: 11:00 AM - 12:30 PM
Location / Meeting Link: EBB 3029/ https://teams.microsoft.com/meet/29121268866024?p=OXphSxoHUWQVis6m5W

Committee Members:
Rafael V. Davalos, PhD (Advisor); David Myers, PhD; Balakrishna Pai, PhD


Title: Understanding cell migration via electrical cues in a tumor-relevant in vitro model

Abstract:
The tumor microenvironment (TME) is a highly dynamic and heterogeneous system in which chemical, electrical, and physical cues collectively regulate immune cell recruitment and cancer progression. Monocyte trafficking toward tumor sites is largely driven by chemokine gradients, particularly CCL2 (C-C motif chemokine ligand 2), which promotes directed migration. Emerging evidence suggests that endogenous bioelectric signals present in a TME (usually between 0.5-2V) may influence cell migration dynamics. Although chemokine signaling is well established as a primary driver of immune cell recruitment, the role of endogenous electrical cues in regulating cell migration within the TME remain poorly characterized. This study presents a tumor-relevant in vitro platform designed to understand how chemotactic and endogenous electric fields (EFs) independently and in combination regulate monocyte migration across a physiologically relevant vascular barrier. A transwell-based system was employed to model transendothelial migration, using a 3µm collagen-coated porous membrane to mimic in vivo leaky tumor vasculature. The extracellular matrix (ECM) and vascular barrier were represented by a monolayer of HUVECs (Human Umbilical Vein Endothelial Cells), and the human monocytic THP-1 cell line was used as a model for circulating monocytes. Transendothelial electrical resistance (TEER) measurements were taken at 48 and 72 hours to confirm barrier integrity, with resistance values observed between 40–55 Ω·cm², consistent with the reduced resistance characteristic of leaky tumor vasculature. Baseline chemotactic responses were established by quantifying THP-1 migration toward a 10 µg/mL CCL2 gradient at 6 h and 24 h timepoints. Controlled EF stimulation was applied across the migration platform for 6 hours. Experiments were conducted under forward- and reversed-polarity direct current (DC) at 1.5 V and alternating current (AC) with a root mean square (RMS) voltage of 1.5 V at 1 Hz. Finally, experiments were performed combining simultaneous exposure to CCL2 and EF, allowing study of independent and synergistic contributions of chemotactic and electrotactic cues. Cellular migration under all these conditions was quantified using fluorescence imaging and cell counting. Baseline migration of THP-1 cells under exposure to 10 µg/mL CCL2 gradient increased migration with ~1.5-fold increase at 6 h and ~1.8-fold increase at 24 h relative to control. Forward-polarity DC also increased migration compared to control, with reversed-polarity DC resulting in a ~1.5- fold increase compared to forward-polarity DC, indicating that field polarity influences electrotactic migration. AC also demonstrated migration effects, though the magnitude of this response was lower than that observed under DC field conditions, suggesting reduced migratory stimulation under oscillating fields. Combined exposure to CCL2 and EF stimulation resulted in the highest migration, with forward-polarity DC + CCL2 producing ~5.5-fold increase, reversed DC + CCL2 with ~10-fold, and AC + CCL2 with ~4-fold increase relative to control. Results show that chemokine gradients primarily guide migration direction, while endogenous EFs modulate migration intensity, establishing the roles of biochemical and bioelectrical signals in regulating monocyte trafficking. This work is thus able to allow for a tunable in vitro model for understanding better about the role of endogenous EFs as modulators of cell behavior within the TME.