A hydrodynamic mechanosensory hypothesis for brush border microvilli

In the proximal tubule of the kidney, Na+ and HCO3- reabsorption vary propo rtionally with changes in axial flow rate. This feature is a critical compo nent of glomerulotubular balance, but the basic mechanism by which the tubu le epithelial cells sense axial flow remains unexplained. We propose that t he microvilli, which constitute the brush border, are physically suitable t o act as a mechanosensor of fluid flow. To examine this hypothesis quantita tively, we have developed an elastohydrodynamic model to predict the forces and torques along each microvillus and its resulting elastic bending defor mation. This model indicates that: 1) the spacing of the microvilli is so d ense that there is virtually no axial velocity within the brush border and that drag forces on the microvilli are at least 200 times greater than the shear force on the cell's apical membrane at the base of the microvilli; 2) of the total drag on a 2.5-mu m microvillus, 74% appears within 0.2 mu m f rom the tip; and 3) assuming that the structural strength of the microvillu s derives from its axial actin filaments, then a luminal fluid flow of 30 n l/min produces a deflection of the microvillus tip which varies from about 1 to 5% of its 90-nm diameter, depending on the microvilli length. The micr ovilli thus appear as a set of stiff bristles, in a configuration in which changes in drag will produce maximal torque.