Mechanotransduction and Flow across the Endothelial Glycocalyx

• Published in: Proceedings of the National Academy of Sciences - PNAS 2003-06, Vol.100 (13), p.7988-7995
• Main Authors: Weinbaum, Sheldon, Zhang, Xiaobing, Han, Yuefeng, Vink, Hans, Cowin, Stephen C.
• Format: Article
• Language: English
• Subjects: Actins; Actins - metabolism; Animals; Bending; Biological Sciences; Blood Flow Velocity; Capillaries - metabolism; Capillary Permeability; Cell membranes; Cellular biology; Cytoskeleton - metabolism; Deformation; Endothelium - anatomy & histology; Endothelium - metabolism; Erythrocyte Deformability; Erythrocytes - physiology; Glycocalyx; Glycocalyx - metabolism; Glycocalyx - physiology; Humans; Leukocytes - physiology; Matrix; Microvilli; Modeling; Models, Biological; Models, Theoretical; Molecular biology; Prevention; Protein Transport; Shear stress; Signal Transduction; Space life sciences; Stress, Mechanical; Structural deflection; Surface layers; Time Factors; Water - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1332808100

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. [Squire, J. M., Chew, M., Nneji, G., Neal, C., Barry, J. & Michel, C. (2001) J. Struct. 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.