(593ar) Extracellular Chemical Stimuli and Mechanotransduction

Mechanical force transduction, or mechanotransduction, has been shown to play an important role in cellular response. In endothelial cells, mechanical force, in the form of shear stress, has been shown to cause cytoskeletal reorganization with an increase in the size and number of actin fibers. More recently, the mechanical connection between the cytoskeleton and the nucleoskeleton has been elucidated.

We have shown that removal of the actin cytoskeleton, via latrunculin A, results in altered nuclear morphology. Increasing latrunculin A concentration results in a decrease in actin cytoskeleton. With decreasing actin cytoskeleton, we observed decreasing nuclear area and decreasing nuclear circularity. Between the control and the highest treatment concentration (100nM Latrunculin A, 3 hours), the difference in both nuclear area and circularity was found to be statistically different with an alpha of 0.001. Nuclear morphology was measured with automated image processing, and allowed data sets in excess of 600 nuclei.

Collaboration with the Bioimage Informatics Department will allow precise quantitation of actin stress fibers in treated and untreated cells, using fiber quantity and length as metrics. This will allow combination of the large nuclear morphology data with a quantitative measurement of actin.