Biomechanical properties of endothelial glycocalyx: An imperfect pendulum

Abstract

Endothelial glycocalyx plays a crucial role in hemodynamics in health and disease, yet studying it is met by multiple technical hindrances. We attempted to outline our views on some biomechanical properties of endothelial glycocalyx, which are potentially amenable to mathematical modeling. We start with the null-hypothesis ascribing to glycocalyx the properties of a pendulum and reject this hypothesis on the grounds of multiple obstacles for pendulum behavior, such as rich decoration with flexible negatively charged side-chains, variable length and density, fluid fixation to the plasma membrane. We next analyze the current views on membrane attachments to the cortical actin web, its pulsatile contraction-relaxation cycles which rebound to the changes in tension of the plasma membrane. Based on this, we consider the outside-in signaling, the basis for mechanotransduction, and the dampening action of the inside-out signaling. The aperiodic oscillatory motions of glycocalyx and cortical actin web underlie our prediction of two functional pacemakers. We next advance an idea that the glycocalyx, plasma membrane, and cortical actin web represent a structure-functional unit and propose the concept of tensegrity model. Finally, we present our recent data suggesting that erythrocytes are gliding or hovering and rotating over the surface of intact glycocalyx, whereas the rotational and hovering components of their passage along the capillaries are lost when glycocalyx of either is degraded. These insights into the mechanics of endothelial glycocalyx motions may be of value in crosspollination between biomechanics, physiology, and pathophysiology for deeper appreciation of its rich untapped resources in health and pharmacotherapy in disease.

Keywords: Cortical actin; Endothelium; Oscillations; Plasma membrane; Red blood cell.

Fig. 1

Oscillation of GAG chains at varying GAG geometries (modified from Ref. with permission.) In contrast to the classical unhindered pendulum oscillations, in the case of glycocalyx motility is modified by the length and density of heparan sulfate chains, as well as the same parameters of the core protein, e.g., syndecans. Vortices are expected to appear at the sites of shed proteoglycans, thus further disorganizing the oscillatory pattern.

Fig. 2

Spatial relations between and dimensions of glycocalyx, lipid-rich domains of the plasma membrane, and cortical actin meshwork. (Note: dimensions are not to scale.)

Fig. 3

Schematic presentation of the ideas of outside-in signaling central to mechanotransduction (panel a) and a reciprocal inside-out signaling essential for signal termination allowing to start the cycle anew (panel c). FGF in panels a and c represents FGF-2. See the text for details. Panel b illustrates the idea of interconnectedness of signaling components with a universal joint shaft.

Fig. 4

Tensegrity model of the intrinsically interactive unit of glycocalyx – plasma membrane – cortical actin. Individual components of this unit are schematically displayed as containers with the fluid exchange between them, resulting in overflow and spillage to the lower container. Contraction-relaxation cycles of the container representing cortical actomyosin squeezes or retracts the back-flow to the upper containers, thus accomplishing feedback regulation.

Fig. 5

Gliding (hovering) and rotation of RBC passaging capillary beds with intact glycocalyx and the loss of the lifting and rotational momentum in vessels with damaged glycocalyx.