Glycocalyx Mediated Mechanotransduction The endothelial glycocalyx is a carbohydrate rich collection of proteoglycans, glycoproteins, complexed sugars, and other soluble components produced by endothelial cells themselves or found dissolved in plasma. Together proteoglycans and glycoproteins form a mesh like structure anchored to the enothelial cell membrane via their core amino-acid constituants. Plasma and endothelial cell derrived componants become entrapped in this mesh in a dynamic equilibrium, which continuously affects the composition and overall thickness of the glycocalyx itself. Thicknesses range from 0.5 µm in muscle capillaries to 2-3 µm in small arteries to 4.5 µm in the carotid arteries. The glycocalyx is continuously involved in shear and enzyme mediated shedding which is dynamically balanced by biosynthesis. As such, the glycocalyx is difficult to define geometrically, as bound molecules are constantly being replaced and there is little distinction between locally synthesized and plasma transported  elements. Structurally, the glycolalyx resembles a self organizing 3D polymer network. Interestingly, enzymatic removal of any constituent greatly affects glycocalyx properties. Thus, any consideration of glycocalyx function must view the structure as a whole including: synergistic effects among its members. The glycocalyx has been implicated in a number of physiological functions, here we shall consider its role as a mechano-transducer.1 The “Bumper Car Model” proposed by D.C. Spray et. al. relies on difficult to visualize actin structures directly beneath the plasma membrane, the actin cortical web (ACW) and dense peripheral actin bands (DPAB). The ACW is a quasiperiodic, geodesic like structure of hexagonally arranged filimentous actin forming a cortical web. Evidence exists that this is the anchoring stucture to which glycocalyx core proteins are attached. DPAB run along the inner plasma membrane parallel to the substrate to which the cells are attached. In the “Bumper Car Model”, the DPAB is a relatively free floating structure loosely attached to stress fibers, focal adhesions and the ACW. It functions like the bumper on a bumper car constantly engaging in small collisions with its neighbors. Under static fluid conditions or at steady state, the DPAB is kept in register with the DPAB of neighboring cell through weak cadherin associations. These linkagages are sufficient for small flow pertubations as the DPAB protects cells from collisions in areas unprotected by the DPAB. The DPAB and ACW are thought to act as a single unit that can undergo only minor rotations about axes parallel to the cell surface. Stress fibers attach the DPAB to focal adhesions only weakly. When forces and torques induced by DPAB rotation are greater than these stress fibers, they rupture along with the DPAB which increases intracellular actin concentrations. The actin monomers are then recruited to form new stress fibers needed to stablize the cell during a time where cell morphology is changing dramatically. The core proteins of the glycocalyx are thought of as bristles in a brush, which “bend in the wind” so to speak, inducing a moment of rotation in the DPAB structure. Individually these moments are small, but collectively they become great enough to disrupt the DPAB for a given threshold shear stress.2 -------------------------------------------------------------------------------------------------------------- 1. Sietze Reitsma, Dick W. Slaaf, Hans Vink, Mara A. M. J. wan Zandvoort, and Mirjam G. A. oude Engbrink. "The endothelial glycocalyx: composition, functions, and visualization." European Journal of Physiology (2007) 454:345-359 2. Mia M. Thi, John M. Tarbell, Sheldon Weinbaum, and David C. Spray. "The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A 'bumper-car' model." PNAS November 23, 2004 vol. 101 no. 47 16483-16488

This page was last edited 10 June 2008