cortical actin nanodynamics determines nitric oxide release in vascular endothelium皮质肌动蛋白nanodynamics决定在血管内皮一氧化氮释放.pdfVIP

Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium Johannes Fels*, Pia Jeggle, Kristina Kusche-Vihrog, Hans Oberleithner Institute of Physiology II, University of Muenster, Muenster, Germany Abstract The release of the main vasodilator nitric oxide (NO) by the endothelial NO synthase (eNOS) is a hallmark of endothelial function. We aim at elucidating the underlying mechanism how eNOS activity depends on cortical stiffness (Kcortex) of living endothelial cells. It is hypothesized that cortical actin dynamics determines Kcortex and directly influences eNOS activity. By combined atomic force microscopy and fluorescence imaging we generated mechanical and optical sections of single living cells. This approach allows the discrimination between Kcortex and bulk cell stiffness (Kbulk) and, additionally, the simultaneous analysis of submembranous actin web dynamics. We show that Kcortex softens when cortical F-actin depolymerizes and that this shift from a gel-like stiff cortex to a soft G-actin rich layer, triggers the stiffness-sensitive eNOS activity. The results implicate that stiffness changes in the ,100 nm phase of the submembranous actin web, without affecting Kbulk, regulate NO release and thus determines endothelial function. Citation: Fels J, Jeggle P, Kusche-Vihrog K, Oberleithner H (2012) Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium. PLoS ONE 7(7): e41520. doi:10.1371/journal.pone.0041520 Editor: David D. Roberts, Center for Cancer Research, National Cancer Institute, United States of America Received April 4, 2012; Accepted June 21, 2012; Published July 23, 2012 Copyright: 2012 Fels et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unre