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Articles 1 - 8 of 8

Full-Text Articles in Biomedical Engineering and Bioengineering

An An Vitro And In Silico Investigation Of The Role Of Nmda Receptor Subtypes Following Mechanical Injury, Pallab Singh Aug 2011

An An Vitro And In Silico Investigation Of The Role Of Nmda Receptor Subtypes Following Mechanical Injury, Pallab Singh

Publicly Accessible Penn Dissertations

The N-methyl D-aspartate receptor (NMDAR), a common glutamate receptor found throughout the brain, has long been implicated as the major mediator of the pathology seen after traumatic brain injury (TBI). However, given their critical role in physiologic function of neural networks, complete inhibition of these receptors is an unsuitable therapeutic strategy. Thus, further investigation into how these receptors respond to injury is required to identify more directed therapeutic targets. Here, we aimed to use two unique experimental models to further investigate the role of NMDARs in the neuronal response to TBI, with specific emphasis on the contribution of different NMDAR ...


Regulation Of Tgf-Β1-Induced Apoptosis And Epithelial-Mesenchymal Transition By Matrix Rigidity, Jennifer L. Leight May 2011

Regulation Of Tgf-Β1-Induced Apoptosis And Epithelial-Mesenchymal Transition By Matrix Rigidity, Jennifer L. Leight

Publicly Accessible Penn Dissertations

Transforming growth factor-β (TGF-β) plays an important role in several diseases that characteristically involve changes in tissue rigidity, such as cancer and tissue fibrosis. To determine whether matrix rigidity regulates the effects of TGF-β, we examined NMuMG and MDCK epithelial cells cultured on polyacrylamide gels with varying rigidity and treated with TGF-β1. Decreasing matrix rigidity reduced cell spreading and increased TGF-β1-induced apoptosis, while increasing matrix rigidity resulted in epithelial-mesenchymal transition (EMT). To more carefully control cell spreading, microcontact printing was used to restrict ECM area and revealed that reducing cell spreading also increased apoptosis. Apoptosis on compliant substrates was associated ...


Unveiling The Molecular Mechanisms Regulating The Activation Of The Erbb Family Receptors At Atomic Resolution Through Molecular Modeling And Simulations, Andrew Shih May 2011

Unveiling The Molecular Mechanisms Regulating The Activation Of The Erbb Family Receptors At Atomic Resolution Through Molecular Modeling And Simulations, Andrew Shih

Publicly Accessible Penn Dissertations

The EGFR/ErbB/HER family of kinases contains four homologous receptor tyrosine kinases that are important regulatory elements in key signaling pathways. To elucidate the atomistic mechanisms of dimerization-dependent activation in the ErbB family, we have performed molecular dynamics simulations of the intracellular kinase domains of the four members of the ErbB family (those with known kinase activity), namely EGFR, ErbB2 (HER2) and ErbB4 (HER4) as well as ErbB3 (HER3), an assumed pseudokinase, in different molecular contexts: monomer vs. dimer, wildtype vs. mutant. Using bioinformatics and fluctuation analyses of the molecular dynamics trajectories, we relate sequence similarities to correspondence of ...


Development As A New Paradigm For Improved Tendon Healing: A Characterization Of Neonatal Tendon Development, Healing During Development And An Investigation Into Differential Parameters During Accelerated Healing, Heather L. Ansorge Dec 2010

Development As A New Paradigm For Improved Tendon Healing: A Characterization Of Neonatal Tendon Development, Healing During Development And An Investigation Into Differential Parameters During Accelerated Healing, Heather L. Ansorge

Publicly Accessible Penn Dissertations

During neonatal development, tendons undergo a well orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but in this case, a mechanically inferior tendon is produced. An injured tendon that is mechanically inferior has compromised function and reruptures after treatment are commonly observed clinically. As a result, the process of development has been postulated as a potential paradigm through which improved adult tissue healing may occur. First, the role of CD44 in healing was examined through a patellar tendon injury in ...


Mammary Epithelial Metastatic Phenotype Forced Through The Extracellular Matrix, Olga Shebanova Dec 2010

Mammary Epithelial Metastatic Phenotype Forced Through The Extracellular Matrix, Olga Shebanova

Publicly Accessible Penn Dissertations

Biochemical and mechanical cues of the extracellular matrix have been shown to play important roles in cell-matrix and cell-cell interactions. We have experimentally tested the combined influence of these cues on cell motility, cell-cell interaction and assembly and traction force profile in an in vitro breast cancer model. The behavior of non-tumorigenic mammary epithelial cells was observed on surfaces with varying ligand concentration and polyacrylamide gel rigidity. Our data shows that cell velocity is biphasic in both matrix rigidity and adhesiveness, which are inversely related. Traction force microscopy revealed that maximum migration velocity is reached at intermediate force of single ...


A Microfabrication Approach To Multicellular Mechanics, Zhijun Liu May 2010

A Microfabrication Approach To Multicellular Mechanics, Zhijun Liu

Publicly Accessible Penn Dissertations

To address the question of how cell-generated forces regulate the organization and function of endothelial cells, I investigated the mechanical forces in a simple model of cell-cell contact: paired cells contacting each other via a single cell-cell junction. To study the responsiveness of AJs to force, I adapted a system of microfabricated force sensors to quantitatively report both the cell-cell tugging force and the size of adherens junctions (AJ). I observed that AJ size was modulated by tugging force: AJs and tugging force grew or decayed with myosin activation or inhibition, respectively. This myosin-dependent regulation operated in concert with a ...


A Systems Approach To Cellular Signal Transduction, Jeremy E. Purvis Aug 2009

A Systems Approach To Cellular Signal Transduction, Jeremy E. Purvis

Publicly Accessible Penn Dissertations

Vital cellular processes such as growth, gene expression, and homeostasis depend on the correct transmission of molecular signals within and between cells. The vast complexity of these molecular signaling networks has necessitated the use of mathematical methods to model, characterize, and predict cellular responses. The work presented in this dissertation shows how computational methods were used to elucidate two clinically-relevant cellular signaling responses: (i) phosphotyrosine signaling through the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that is commonly overexpressed or structurally altered in human cancers; and (ii) phosphoinositide and calcium signaling in human platelets---the key cellular mediators of ...


Mechanical And Chemical Effects In Adhesion Of Thin Shell Structures With Applications In Wafer Bonding And Adhesion Of Living Cells, Richard M. Springman Aug 2009

Mechanical And Chemical Effects In Adhesion Of Thin Shell Structures With Applications In Wafer Bonding And Adhesion Of Living Cells, Richard M. Springman

Publicly Accessible Penn Dissertations

A theoretical model is analyzed to investigate the adhesion of thin shell structures to both rigid and deformable substrates under a variety of surface conditions. The thermodynamic forces driving the adhesive process are determined from an interfacial free energy, which is described within a classical thermodynamics framework. Deformations of the thin, elastic shells are studied using a geometrically nonlinear shell theory. Finite-range adhesive tractions, chemical segregation, substrate compliance, and substrate topography all are considered over a wide range of geometric and material parameters. Equilibrium adhesion states are characterized by a shell flatness parameter, the contact radius, and the adhesive and ...