Anionic biopolymers as blood flow sensors

Abstract

The finding of flow-dependent vasodilatation rests on the basic observation that with an increase in blood flow the vessels become wider, with a decrease the vascular smooth muscle cells contract. Proteoheparan sulphate could be the sensor macromolecule at the endothelial cell membrane-blood interface, that reacts on the shear stress generated by the flowing blood, and that informs and regulates the vascular smooth muscle cells via a signal transduction chain. This anionic biopolyelectrolyte possesses viscoelastic and specific ion binding properties which allow a change of its configuration in dependence on shear stress and electrostatic charge density. The blood flow sensor undergoes a conformational transition from a random coil to an extended filamentous state with increasing flow, whereby Na⁺ ions from the blood are bound. Owing to the intramolecular elastic recoil forces of proteoheparan sulphate the slowing of a flow rate causes an entropic coiling, the expulsion of Na⁺ ions and thus an interruption of the signal chain. Under physiological conditions, the conformation and Na⁺ binding proved to be extremely Ca²⁺-sensitive while K⁺ and Mg²⁺ ions play a minor role for the susceptibility of the sensor. Via counterion migration of the bound Na⁺ ions along the sensor glycosaminoglycan side chains and following Na⁺ passage through an unspecific ion channel in the endothelial cell membrane, the signal transduction chain leads to a membrane depolarization with Ca²⁺ influx into the cells. This stimulates the EDRF/NO production and release from the endothelial cells. The consequence is vasodilatation.