The focus of the Program Project is to assess the signaling mechanisms and impact of several synergistic biochemical and cellular processes on lung vascular endothelial barrier re-sealing and adherens junction (AJ) assembly in systems ranging from single cells to animal models. The overriding objective of Core D is to define the biophysical and physiological bases of restoration of lung fluid balance in post-inflammatory lung injury. Core D will provide physiological assessment of lung vascular permeability. The Specifc Aims of Core D are: (1) to measure VE-cadherin-mediated adhesion and junctional strengthening and (2) to quantify changes in VE-cadherin affinity, in cell pairs subjected to different treatments described in all Projects; (3) to quantify static and dynamic tension at VE-cadherin junctions in response to treatments described in all Projects; (4) to perform hydraulic pressure-based measurements of endothelial barrier permeability, and (5) to perform transvascular protein and liquid permeability measurements of lung endothelium in vivo and in vitro. To achieve these aims, Dr. Deborah Leckband, Core D leader and expert in mechanobiology and adhesion, will oversee Core D activities related to biophysical analyses of endothelial junctions. Dr. Stephen Vogel, an accomplished pulmonary vascular physiologist, will be responsible for the physiological aspects of Core D centering on lung permeability assessments. The Biophysics and Physiology Core will be essential for meeting the scientific objectives of each Project, because it will allow PIs to quantify the mechanical properties of re-annealing intercellular junctions and to assess how intercellular adhesion and junction tension contribute to lung vascular barrier resealing dynamics. All projects will use all Core D services offered.
Core D Lay Summary Core D's biophysical facility will offer PIs a series of techniques to measure the mechanical strength of the structures that hold together the cells lining lung capillaries. These structures are believed to suffer loss of mechanical strength in lung diseases that cause pulmonary ?vascular leak? leading to gaps between cells, impaired gas exchange and poor clinical outcomes. Vascular leak during various stages of lung vascular injury and repair will be evaluated in Core D's Physiology facility, in which Project PIs will have access to liquid and protein permeability measurements in intact or isolated murine lungs under approved institutional animal protocols.
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