Engineering Commons^™

A Single Cell Pair Mechanical Interrogation Platform To Study Cell-Cell Adhesion Mechanics, Amir Monemianesfahani

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. Perturbations of the cell-cell adhesion structure or relatedmechanotransduction pathways lead to pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been used to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. The current techniques, however, have limitations on their ability to measure the cell-cell adhesion force directly and quantitatively. These methods use a monolayer of cells, which makes it impossible to quantify the forces within a single cell-cell adhesion complex. Other methods using single cells or cell …

Mechanochemical Regulation Of Epithelial Tissue Remodeling: A Multiscale Computational Model Of The Epithelial-Mesenchymal Transition Program, Lewis Scott

Theses and Dissertations

Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, …

Stretch Control Of Adipocyte Insulin Signaling, Tasneem Bouzid

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Obesity and related metabolic disorders have reached global epidemic proportions in recent decades. Excess and hypertrophic adipose tissue has been implicated in the development of various pathological diseases and disorders including Type-2 diabetes mellitus (Type-2 DM). In addition to serving as energy storage for the body, evidence also suggests that adipose tissue behaves as an endocrine organ capable of secreting bioactive cytokines known as adipokines, which mediate insulin signaling pathways in various tissues. Physical exercise has been demonstrated to positively affect insulin signaling activities potentially through increasing the secretion of insulin sensitizing adipokines and/or decreasing the secretion of pro-inflammatory insulin …

Biophysical Tools To Study Cellular Mechanotransduction, Ismeel Muhamed, Farhan Chowdhury, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane's bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na^⁺, Ca²⁺, K^⁺ channels). …

The Role Of Mechanical Loading In Chondrocyte Signaling Pathways, Qiaoqiao Wan

Open Access Dissertations

Chondrocytes are a predominant cell type present in articular cartilage, whose integrity is jeopardized in joint degenerative diseases such as osteoarthritis (OA). In the chondrocytes of patients with OA, the elevated levels of inflammatory cytokines such as interleukin 1β (IL1β) and tumor necrosis factor α (TNFα) have been reported. These cytokines contribute to degradation of cartilage matrix by increasing activities of proteolytic enzymes. In addition to their contribution to proteolytic enzymes, these cytokines adversely affect anabolic activity of chondrocytes by inhibiting the production of proteoglycans and type II collagen. Therefore, blocking the action of these cytokines is a potential strategy …

Three-Dimensional Endothelial Spheroid-Based Investigation Of Pressure-Sensitive Sprout Formation, Min Song

Theses and Dissertations--Biomedical Engineering

This study explored hydrostatic pressure as a mechanobiological parameter to control in vitro endothelial cell tubulogenesis in 3-D hydrogels as a model microvascular tissue engineering approach. For this purpose, the present investigation used an endothelial spheroid model, which we believe is an adaptable microvascularization strategy for many tissue engineering construct designs. We also aimed to identify the operating magnitudes and exposure times for hydrostatic pressure-sensitive sprout formation as well as verify the involvement of VEGFR-3 signaling. For this purpose, we used a custom-designed pressure system and a 3-D endothelial cell spheroid model of sprouting tubulogenesis. We report that an exposure …

The Effect Of Cholesterol On The Osteoblast Responsiveness To Hydrodynamic Pressure Stimulation, Kristen Lough

Theses and Dissertations--Biomedical Engineering

Hypercholesterolemia is a risk factor for osteoporosis but the underlying mechanism is unknown. Previous evidence suggests that osteoporosis results from an impaired regulation of osteoblasts by fluid pressure fluctuations in the bone matrix. Recently, our laboratory showed that enhanced cholesterol in the cell membrane, due to hypercholesterolemia, alters leukocyte mechanosensitivity. We predict a similar link between osteoblasts and hypercholesterolemia leading to osteoporosis. Specifically, we hypothesize that extracellular cholesterol modifies the osteoblast sensitivity to pressure. MC3T3-E1 cells were exposed to hydrodynamic pressures regimes (mean=40mmHg, amplitude=0-20mmHg, frequency=1Hz) for 1-12 hours. To assess the impact of membrane cholesterol enrichment, cells were pre-treated with …

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …

The Effect Of Physiological Cyclic Stretch On The Cell Morphology, Cell Orientation And Protein Expression Of Endothelial Cells, V. Barron, Claire Brougham, K. Coghlan, C. Stenson-Cox, D. O'Mahoney, P.E. Mchugh

Articles

In vivo, endothelial cells are constantly exposed to pulsatile shear and tensile stresses. The main aim of this study was to design and build a physiological simulator, which reproduced homogenous strain profiles of the tensile strain experienced in vivo, and to investigate the effect of this cyclic tensile strain on the cell morphology, cell orientation and protein expression of endothelial cells. The biological response of human umbilical vein endothelial cells to a uniaxial cyclic stretch, in this newly developed simulator, was examined experimentally using immunohistostaining and confocal imaging and it was

found that the cells elongated and oriented at 58.9± …

Mechano-Biological Interactions Of Endothelial Cells, Claire Brougham, Karen Coughlan, Valerie Barron, Peter Mchugh

Conference Papers

Atherosclerosis is an ever-increasing cause of morbidity in the western world. Current surgical treatments include bypass grafts and coronary artery stents. However, there is still a need for alternative approaches especially for those who cannot receive conventional therapy. Tissue engineering is one such approach that may hold the key to the repair and regeneration. Tissue engineering is one such approach that may hold the key to the repair and regeneration of coronary arteries. Nevertheless, many questions need to be answered before a vialbe vascular tissie with the inherent properties of native tissue becomes a real contender with the surgical therapies …