Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds

Abstract

Endothelial and epithelial barrier disruptions are detected via local decrease in cellular tension, which are coupled to reactive oxygen species–dependent self-restorative actin remodeling dynamics.

Blood cells and endothelial barrier function

“…83,94 It has also been reported that the endothelial barrier dysruption caused by transmigrating leukocytes are detected by the endothelial cells as a release of isometric tension, which results in protective actin remodeling that is dependent on the production of reactive oxygen species. 95 Furthermore, the results of a recent study reveal that extravasating leukocytes deposit microparticles on the subendothelium during their passage through the junctions and that the microparticle deposition serves to maintain barrier function; inhibition of neutrophil-derived microparticle formation resulted in dramatically increased vascular leakage. 96 Another consequence of neutrophil activation within the microcirculation is capillary no-reflow, which is manifested as a reduced number of perfused capillaries and tissue hypoxia.…”

Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

“…A recent study suggests that ventral lamellipodia generated from pre-existing actin filaments close these small, micrometer-scale pores (Martinelli et al, 2013). Barrier disruption is recognized by the endothelium as the localized loss of isometric tension and force unloading that induces F-actin remodeling, which depends on Rac1, Arp2/3 and reactive oxygen species, and the formation of membrane protrusions in order to close the pore.…”

Dynamics between actin and the VE-cadherin/catenin complex

“…11 Gap formation was also demonstrated using N-WASP mutants 11,21 or depletion of cortactin, 85 molecules that to the end control the activity of the ARP2/3 complex. 113,114 Although the molecular mechanisms that control interaction between JAIL formation and VE-cadherin-mediated cell adhesion is incompletely understood there is evidence that α-catenin and p120 ctn , components of the VE-cadherin/catenin complex, are interaction partners for molecules that control actin polymerization. In particular, vinculin is associated with the cadherin/ catenin complex, 56 and was indicated to couple actin stress fibers to the VE-cadherin/catenin complex in endothelium.…”

“…In addition, a recent paper suggested a tension-dependent recovery of microwounds that develop due to leukocyte transmigration or after mechanical wounding by actin-driven and ARP2/3-dependent formation of lamellipodia-like structures that appeared quickly after wounding and were termed ventral lamellipodia. 113 Those actin-rich structures were also responsible for closing transcellular wounds, and are mostly independent on cadherin-mediated cell adhesion. 113 It has to be investigated if, apart from loss of tension, other mechanisms play a role.…”

“…113 Those actin-rich structures were also responsible for closing transcellular wounds, and are mostly independent on cadherin-mediated cell adhesion. 113 It has to be investigated if, apart from loss of tension, other mechanisms play a role. It is reasonable to assume that those transcellular wounds disintegrate both the membrane cytoskeleton and cortical actin filaments, and thus, might lead to actin nucleation which in turn might drive wound closure.…”