On the way to subcellular imaging of mechanotransduction in the developing vasculature
2007
Endothelial cells that comprise vessels and line the heart are known to respond to mechanical forces imparted
by fluid flow. It is also known that blood flow is required for vascular remodeling and that abnormal heart contractions
lead to the failure of the vasculature to remodel properly. Although there is considerable evidence to indicate that flow is
necessary, little is known about how mechanical signals are transduced in endothelial cells in the embryo. This project is
focused on understanding the role mechanical forces play in the development of the cardiovascular system using recently
generated FRET (Fluorescence Resonance Energy Transfer) reporter that can detect real-time Src-kinase activity in cells
using fluorescence microscopy. Src kinase regulates integrin-cytoskeleton interactions that are essential for
mechanotransduction, and its activity is upregulated in cultured endothelial cells exposed to flow. Experiments reported
here were focused on testing potential feasibility of the proposed technique to sense Src changes in vivo. Successful
implementation of this project will reveal previously unknown signaling events involved in the mechanism of vascular
remodeling and their relation to the blood flow, thus providing a unique tool for in vivo sub-cellular imaging of
mechanotransduction in the vasculature and other organs.
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