Biomechanics and Biotransport Commons^™

Intercellular Stress Generation During 1d Collective Migration Of Cancer Cells, Logan Waddle

Physics Undergraduate Honors Theses

Physical forces drive many cellular processes such as migration and proliferation. A metastatic tumor will have invasive strands/chains that extend from the main tumor. These chains of cells collectively migrate away from the main tumor to establish new colonies elsewhere in the body. However, how physical forces drive this collective invasion and the required energy for this process is not well understood. Invasion of a metastatic tumor to surrounding tissues leads to a majority of cancer-associated death and is often a collective effort among cells, it is therefore important to fully understand the process behind collective cancer invasion.

The goal …

Traction Force Microscopy Using An Epifluorescence Microscope: Experimental Considerations And Caveats, Zaria Booth, Mazen Mezher, Rudra Patel, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

Forces exerted by cells due to their internal contractility play fundamental roles in a host of processes, including adhesion, migration, survival and differentiation. Traction force microscopy (TFM) enables the determination of forces exerted by cells or cell collectives on their environment, which is typically taken to be an extra-cellular matrix (ECM)-coated substrate. Sample preparation for TFM involves the plating of cells onto an environment embedded with fiducial markers. The imaging of these fiducial markers in the presence and absence of the cells then enables calculation of the displacement of localized regions of the environment, and, consequently, the spatial distribution of …

The Sexually Dimorphic Role Of Connexin 43 In Bone Remodeling And Disuse-Induced Bone Loss, Gabriel A. Hoppock

Theses and Dissertations

Bone loss is frequently experienced by individuals undergoing long-term disuse, such as prolonged bedrest, immobilization due to paralysis or injury, and conditions such as spaceflight. Under normal physiological conditions, bone remodeling is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts, and the activity of osteoblasts and osteoclasts is orchestrated by osteocytes. Osteocytes are the most abundant cell type found in bone and ample evidence suggests they are bone’s main mechanosensory cell type. Therefore, understanding osteocyte biology and responses to mechanical signals, or lack thereof during unloading, may lead to new therapeutic targets to combat bone loss during disuse. Previous data has …

Development And Application Of A Microfluidic Platform For Quantifying Intra-Tumoral Compressive Stress., Zachary P. Fowler

Electronic Theses and Dissertations

Cancer progression is linked to the emergence of aberrant mechanical signaling in the tumor microenvironment. Modulation of extrinsic signals, such as ECM stiffness and composition, have been thoroughly explored. However, the development of solid stresses within the tumor remains poorly understood. To address this, we have developed a microfluidic platform that generates deformable alginate microbeads that allow for the quantification of compressive stresses generated within a growing glioblastoma (GBM) tumorsphere. PDMS microfluidic devices were fabricated via SU-8 mold with channels ranging from 10µm-40µm in diameter. Fluorescently labeled sodium alginate underwent a cross-linking reaction within the device to generate monodisperse beads …

A Magneto-Rheological Platform To Dynamically Control Afterload In Engineered Micro Heart Muscles, David Schuftan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiovascular disease is the leading cause of death is the United States, accounting for nearly 1 in 5 deaths. Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, how these mechanical forces exactly affect the cellular biology of the heart is not well defined. In vitro models using cardiomyocytes derived from human induced pluripotent stem cells enable researchers to develop medium throughput systems to study cardiac mechanobiology at the cellular level. Previous models have been developed to enable the study of mechanical forces such as cardiac afterload. However, most of these models require …

Blood Flow Regulates Atherosclerosis Progression And Regression, Morgan A. Schake

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

Atherosclerosis is the most prevalent pathology of cardiovascular disease with no known cure. Despite the many systemic risk factors for atherosclerosis, plaques do not form randomly in the vasculature. Instead, they form around bifurcations and the inner curvature of highly curving arterial segments that contain so-called disturbed blood flow that is low in magnitude and multidirectional over the cardiac cycle. Conversely, straight, non-bifurcated arterial segments that contain moderate-to-high and unidirectional (i.e., normal) blood flow are protected from plaque development. Thus, blood flow is a key regulator of atherosclerosis that may be able to be leveraged to develop new therapeutics. Towards …

Mechanically Driven In Vivo Osteocyte Ca2+ Signaling: Aging And Pharmacologic Effects, James Padgett

Dissertations and Theses

Bone’s ability to respond and adapt to mechanical loading declines significantly with age which is a major contributor to bone fragility. It is widely accepted that osteocytes are the key cells responsible for orchestrating the development of the “ideal” skeleton. This ability is attributed to osteocyte’s role as the primary mechanosensing cell that is responsible for maintaining the skeleton’s integrity throughout life. Recent work from our laboratory has shed light into how osteocytes respond to mechanical loading in vivo. The breakthrough approaches that enabled these discoveries were development of: (1) the first ever reporter mouse model with a genetically encoded …

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 …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …