Blood-flow sensing by anionic biopolymers.

Abstract

Using 23Na-NMR techniques we could show that the polyanion proteoheparan sulfate integrated into the membrane of endothelial cells may serve as "flow sensor'. Based on its viscoelastic properties, heparan sulfate proteoglycan is present as a random coil under "no flow' conditions, whereby most of its polyanionic sites undergo intramolecular hydrogen bonding. With increasing flow the macromolecule becomes unfolded into a filamentous structure. Additional anionic binding sites to which Na+ ions from the blood bind are released by this shear stress-dependent conformational change. The Na+ binding triggers the signal transduction chain for a vasodilatory vessel reaction. Decrease in flow effects, for reasons of the intramolecular elastic recoil forces of the macromolecules, an entropic coiling, the release of Na+ ions and thus an interruption of the signal chain. Proteoheparan sulfate adsorbed onto a hydrophobic surface in physiological Krebs solution at pH 7.3 demonstrated clearly its characteristic as a Na+ sensor. While Ca2+ ions modulated the adsorption (promotion with increasing Ca2+ concentrations) by changing the conformation of the sensor molecule, the adsorbed amount was determined preferably by the Na+ concentration. K+ and Mg2+ ions showed slightly desorbing properties with increasing concentrations. Thus, it may be concluded that Na+ ions play the role as "first messenger' in flow-dependent vasodilation.