‘Tenertaxis’: lymphocytes seeking the easy road

Leukocyte trafficking across the endothelium, which can occur by either the transcellular or the paracellular route, has been well studied in terms of biochemical inputs such as chemoattractants and adhesion molecules. The mechanisms that control the actual breaching of the endothelial barrier (i.e. diapedesis), however, are still unclear. Some investigators have considered that basic biomechanical features such as endothelial cell stiffness might be involved, and others have suggested that sites of leukocyte diapedesis might simply represent the path of least resistance. On page 3720, Roberta Martinelli, Christopher Carman, John Greenwood and colleagues investigate the role of barrier biomechanics in lymphocyte diapedesis. The authors found that increasing junctional integrity caused a shift towards transcellular diapedesis, whereas decreasing junctional integrity was associated with more paracellular diapedesis. These shifts did not alter the overall efficiency of diapedesis or the levels or distribution of adhesion molecules. The authors next sought to examine how lymphocytes might perceive changes in junctional strength. They show invadosome/podosome-like protrusions (ILPs) extending from lymphocytes that appear to probe the vascular endothelium during lateral migration; further experiments led the authors to suggest that ILPs might be sampling the stiffness of the endothelium. Moreover, they show that the efficiency of diapedesis correlated inversely with local F-actin density and stiffness. The authors have therefore demonstrated that the route preference for lymphocyte migration can be switched, and have defined an active process of seeking out the ‘path of least resistance’ for lymphocyte diapedesis, which they call ‘tenertaxis’.