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Full-Text Articles in Biomedical Engineering and Bioengineering

Quantitative Elucidation Of A Distinct Spatial Gradient-Sensing Mechanism In Fibroblasts, Ian C. Schneider, Jason M. Haugh Dec 2005

Quantitative Elucidation Of A Distinct Spatial Gradient-Sensing Mechanism In Fibroblasts, Ian C. Schneider, Jason M. Haugh

Ian C. Schneider

Migration of eukaryotic cells toward a chemoattractant often relies on their ability to distinguish receptor-mediated signaling at different subcellular locations, a phenomenon known as spatial sensing. A prominent example that is seen during wound healing is fibroblast migration in platelet-derived growth factor (PDGF) gradients. As in the well-characterized chemotactic cells Dictyostelium discoideum and neutrophils, signaling to the cytoskeleton via the phosphoinositide 3-kinase pathway in fibroblasts is spatially polarized by a PDGF gradient; however, the sensitivity of this process and how it is regulated are unknown. Through a quantitative analysis of mathematical models and live cell total internal reflection fluorescence microscopy ...


Spatial Analysis Of 3′ Phosphoinositide Signaling In Living Fibroblasts, Iii: Influence Of Cell Morphology And Morphological Polarity, Ian C. Schneider, Elizabeth M. Parrish, Jason M. Haugh Aug 2005

Spatial Analysis Of 3′ Phosphoinositide Signaling In Living Fibroblasts, Iii: Influence Of Cell Morphology And Morphological Polarity, Ian C. Schneider, Elizabeth M. Parrish, Jason M. Haugh

Ian C. Schneider

Activation of phosphoinositide (PI) 3-kinase is a required signaling pathway in fibroblast migration directed by platelet-derived growth factor. The pattern of 3′ PI lipids in the plasma membrane, integrating local Pl 3-kinase activity as well as 3′ PI diffusion and turnover, influences the spatiotemporal regulation of the cytoskeleton. In fibroblasts stimulated uniformly with platelet-derived growth factor, visualized using total internal reflection fluorescence microscopy, we consistently observed localized regions with significantly higher or lower 3′ PI levels than adjacent regions (hot and cold spots, respectively). A typical cell contained multiple hot spots, coinciding with apparent leading edge structures, and at most ...


Spatial Analysis Of 3′ Phosphoinositide Signaling In Living Fibroblasts: Ii. Parameter Estimates For Individual Cells From Experiments, Ian C. Schneider, Jason M. Haugh Jan 2004

Spatial Analysis Of 3′ Phosphoinositide Signaling In Living Fibroblasts: Ii. Parameter Estimates For Individual Cells From Experiments, Ian C. Schneider, Jason M. Haugh

Ian C. Schneider

Fibroblast migration is directed by gradients of platelet-derived growth factor (PDGF) during wound healing. As in other chemotactic systems, it has been shown recently that localized stimulation of intracellular phosphoinositide (PI) 3-kinase activity and production of 3′ PI lipids in the plasma membrane are important events in the signaling of spatially biased motility processes. In turn, 3′ PI localization depends on the effective diffusion coefficient, D, and turnover rate constant, k, of these lipids. Here we present a systematic and direct comparison of mathematical model calculations and experimental measurements to estimate the values of the effective 3′ PI diffusion coefficient ...