No abstract

Over the past decade, since it was first observed in vivo, there has been an explosion in interest in the thin (approximately 500 nm), gel-like endothelial glycocalyx layer (EGL) that coats the luminal surface of blood vessels. In this review, we examine the mechanical and biochemical properties of the EGL and the latest studies on the interactions of this layer with red and white blood cells. This includes its deformation owing to fluid shear stress, its penetration by leukocyte microvilli, and its restorative response after the passage of a white cell in a tightly fitting capillary. We also examine recently discovered functions of the EGL in modulating the oncotic forces that regulate the exchange of water in microvessels and the role of the EGL in transducing fluid shear stress into the intracellular cytoskeleton of endothelial cells, in the initiation of intracellular signaling, and in the inflammatory response.

No abstract

In this inaugural paper, we shall provide an overview of the endothelial surface layer or glycocalyx in several roles: as a transport barrier, as a porous hydrodynamic interface in the motion of red and white cells in microvessels, and as a mechanotransducer of fluid shearing stresses to the actin cortical cytoskeleton of the endothelial cell. These functions will be examined from a new perspective, the quasiperiodic ultrastructural model proposed in Squire et al. Biol. 136, 239 -255] for the 3D organization of the endothelial surface layer and its linkage to the submembranous scaffold. We shall show that the core proteins in the bush-like structures comprising the matrix have a flexural rigidity, EI, that is sufficiently stiff to serve as a molecular filter for plasma proteins and as an exquisitely designed transducer of fluid shearing stresses. However, EI is inadequate to prevent the buckling of these protein structures during the intermittent motion of red cells or the penetration of white cell microvilli. In these cellular interactions, the viscous draining resistance of the matrix is essential for preventing adhesive molecular interactions between proteins in the endothelial membrane and circulating cellular components.A lthough the endothelial surface glycocalyx was first identified by special electron microscopic staining techniques nearly 40 years ago (1), it is only relatively recently that this surface layer has been observed in vivo (2) and the importance of its multifaceted physiological functions recognized. Key among these functions are its role as a molecular sieve in determining the oncotic forces that are established across microvessel endothelium (3-6), its role as a hydrodynamic exclusion layer preventing the interaction of proteins in the red cell and endothelial cell membranes (7-9), its function in modulating leukocyte attachment and rolling (10) and as a transducer of mechanical forces to the intracellular cytoskeleton in the initiation of intracellular signaling, as proposed herein.It is widely recognized that fluid shearing forces acting on endothelial cells (ECs) have a profound effect on EC morphology, structure, and function (11,12). It is now also clear from theoretical considerations (7,9,13,14) that the shear stress at the edge of the endothelial surface layer is greatly attenuated by the extracellular matrix of proteoglycans and glycoproteins in the glycocalyx, with the result that fluid velocities, except near the edge of the layer, are vanishingly small. Thus, the shear stress due to the fluid flow acting on the apical membrane of the EC itself is negligible. This paradoxical prediction has raised a fundamental question as to how hydrodynamic and mechanical forces, more generally, are transmitted across the structural components of the glycocalyx. How do these components deform under the action of these forces, and how are these forces and deformations communicated to the underlying cortical cytoskeleton (CC)?Little was known about the specific proteins or generalized structure...