Mechanics of endothelial cell architecture and vascular permeability

Blood vessel walls form a selective barrier to the transport of materials b etween blood and tissue, and the endothelium contributes significantly to t his barrier function. The role of the endothelium is particularly important in thin-walled vessels, such as venules, because during tissue inflammatio n the endothelial junctions widen in localized areas and gaps form, thus co mpromising the barrier function. The mechanisms of endothelial gap formatio n are still under question. In this review we describe what is known about the structure of endothelial cell-cell junctions and how this structure can change during inflammation. We then consider two possible mechanisms by wh ich endothelial gaps are formed: active endothelial cell contraction or bre akdown of the junctional complex, followed by passive recoil. Using measure d values of the mechanical properties of endothelial cells, and the forces to which they are subjected, we calculate that gap formation by breakdown o f cellular adhesion, followed by passive recoil, is a feasible mechanism. F inally, since endothelial cell surfaces, including junctions, are coated wi th a glycocalyx, we consider the question of whether changes in the glycoca lyx can markedly increase endothelial permeability. We conclude that gap fo rmation can occur by active contraction or by breakdown of adhesion, depend ing on the inflammatory mediator, and that the responses of the glycocalyx may also play an important role in the regulation of microvascular permeabi lity.