Under physiological conditions, vascular endothelial cells (ECs) form a dynamic semi-permeable barrier regulating the movement of water and solutes across nanometer-scale intercellular gaps. Under inflammatory conditions, however, formation of larger (micrometer-scale) EC gaps results in increased vascular leakiness to circulating fluid, proteins, and cells, resulting in organ edema and dysfunction responsible for key pathophysiologic findings in numerous acute and chronic inflammatory disorders.

Our work used atomic force microscopy integrated with optical microscopy to study the dynamic transformations of EC mechanical properties in response to external stimuli (e.g., from biochemical agents that increase or disrupt vascular barrier function). The cover image of the December 19 issue of Biophysical Journal shows a frame from a time-lapse movie of EC gap closure illustrating the motion dynamics of EC lamella, lamellipodia, ruffles, and nuclei and their response to the EC barrier-enhancing sphingolipid, sphingosine-1-phosphate (S1P). The gap was formed by polydimethylsiloxane micropillars inserted in EC cultures. The movie was compiled from a stack of phase microscopy images acquired every 15 seconds for ~3.5 hours, the closure time of that gap. A plot of the gap’s effective diameter versus time shows an increased rate of gap closure after S1P (2 µM) stimulation. The back-and-forth motion of lamella and lamellipodia during gap closure resembles water motion at a riverbank or beach, which motivated our study of the microrheology of EC regions during EC motion.

To find out more on inflammation and our studies of the mechanical aspects of inflammatory diseases at the cellular level, please visit https://scripps.ufl.edu/departments/centers-and-specialties/center-for-inflammation-science-and-systems-medalicine/what-is-inflammation.

— Fernando Teran Arce, Scott Younger, Amir A. Gaber, Joseph B. Mascarenhas, Marisela Rodriguez, Steven M. Dudek, and Joe G.N. Garcia