Abstract

Cells constantly sense and respond to biophysical cues in their microenvironment. Understanding how they interpret these mechanical signals is essential for advancing tissue modeling, studying disease mechanisms, and developing more predictive in vitro platforms. This dissertation presents a series of engineered microphysiological systems (MPS) designed to investigate how mechanical stimuli shape cellular behavior in distinct human tissue microenvironments. In Aim 1, I developed a reconfigurable microfluidic platform that mimics key features of human vascular barriers. This system supports the integration of porous membranes, 3D hydrogels, and flow channels, enabling precise control over both mechanical and biochemical cues. The modularity of the platform allows for flexible adaptation to different tissue types and experimental conditions. Aim 2 introduces a microfluidic approach to engineer collagen fiber alignment interfaces by modulating extensional strain during gel injection. This method enables the creation of localized discontinuities in extracellular matrix (ECM) alignment, allowing investigation of how fiber heterogeneity and interfaces impact directed cell migration. In Aim 3, I examine topographical mechanical memory in mesenchymal stem cells. Using patterned ridge–flat substrates, I show that cells retain migratory behaviors influenced by prior topographical exposure, even after the mechanical cue is removed, suggesting long-lasting cellular memory effects. Finally, Aim 4 explores the independent and synergistic effects of shear stress and topographical cues on endothelial morphology and function. While both cues promote cell alignment, their effects on gene expression are not fully interchangeable, acting independently for some genes and synergistically for others. These findings highlight the complexity of mechanical regulation in vascular biology. Together, these platforms provide versatile tools to probe cellular mechanobiology and significantly enhance the physiological relevance of in vitro models for biomedical research, disease modeling, and therapeutic development.

Library of Congress Subject Headings

Tissue engineering; Cells--Microbiology; Cells--Mechanical properties; Cellular physiology; Cellular interaction

Publication Date

6-2025

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

Campus

RIT – Main Campus

Plan Codes

BMECHE-PHD

Download

Share

COinS