Abstract

Directional migration of cells is one of the most important physiological processes, necessary for tissue and organ development. It also plays a crucial role in pathological conditions such as cancer metastasis. This directed migration is influenced by various factors present in the native environment, which guide cells to migrate steadily in a specific direction. Due to its importance, over the years, a lot of emphasis has been placed on understanding and exploring the biochemical and biophysical factors that direct cell migration. In addition to the commonly studied biochemical and biophysical cues, contact guidance from collagen fibers, in the native matrix, has also been shown to influence cell motility. However, current studies treat the arrangement of collagen fibers in a binary manner, either as unaligned or aligned fibers. In the native matrix, however, these fibers gradually transition from an aligned to an unaligned state, creating a gradient in fiber alignment. Since it is difficult to engineer these fiber alignment gradients at in vivo length scales, their role in guiding cell migration remains unexplored. Understanding how cells sense and respond to these cues is crucial for developing physiologically relevant in vitro models and advancing tissue engineering applications. To address this shortcoming, I first developed a microfluidic device that could replicate collagen fiber alignment gradients at physiologically relevant length scales. Using this microfluidic platform, I investigated the effects of these engineered gradients on both single cells and cell clusters. Both single cells and cell clusters exhibited a preferential migration towards increased fiber alignment. Cancer cells demonstrated a 2.6-fold directional bias, while endothelial cells displayed 2 times higher directional persistence on the fiber alignment gradient. Finally, I employed time-lapse imaging to understand the mechanism behind this preferential migration. Cells seeded on a gradient initially extended protrusions in multiple directions but preferentially stabilized those pointing toward higher alignment, resulting in cell polarization towards regions of increasing alignment. This polarization may be responsible for driving the observed directional migration bias. This work establishes a model system that allows investigation of fiber alignment gradients as a potent guidance cue for directed cell migration. Furthermore, this microfluidic device is a versatile platform that can be easily modified to incorporate additional native gradients. This can facilitate studies on how cells interpret simultaneous multiple directional cues.

Library of Congress Subject Headings

Collagen--Synthesis; Tissue engineering; Cell migration; Cell physiology; Cell interaction

Publication Date

8-2025

Document Type

Dissertation

Student Type

Graduate

Degree Name

Biomedical and Chemical Engineering (Ph.D)

Department, Program, or Center

Biomedical Engineering

College

Kate Gleason College of Engineering

Advisor

Vinay Abhyankar

Advisor/Committee Member

Karin Wuertz-Kozak

Advisor/Committee Member

Christopher Lewis

Campus

RIT – Main Campus

Plan Codes

BMECHE-PHD

Download

Share

COinS