Mechanical Coupling of the Endothelial Cytoskeleton and Nucleus with VEGF Stimulation

Vascular endothelial growth factor (VEGF) induces endothelial cell proliferation, migration, and a host of cellular responses that are necessary for angiogenesis. The effects of VEGF on gene expression in endothelial cells have been well characterized, and many of the chemical pathways have been elucidated. Similarly, VEGF is known to impact cytoskeletal structure and cellular motility. Here, we show that VEGF influences cytoskeletal-nuclear interaction by imaging human umbilical vein endothelial cells treated with VEGF. We visualize increased actin fibers present at the nucleus in VEGF treated cells. We also quantify increased fluctuations at the nuclear envelope with VEGF-treatment. This manifests itself as both a gross nuclear fluctuations, quantifiable as changes in nuclear area, and fine fluctuations, which can be visualized over several hours. Further, we observe an increase in intranuclear velocity of chromatin-bound probes. Our findings suggest enhanced mechanical coupling between the cytoskeleton and nucleus under VEGF treatment, which may have implications in the mechanobiology of altered gene expression during angiogenesis.