A Time-Dependent Electrodiffusion-Convection Model for Charged Macromolecule Transport Across the Microvessel Wall and in the Interstitial Space

Abstract

The extravascular matrix carries negative charge due to its glycosaminoglycans (GAGs) composition. Previous experiments have demonstrated that the negative charge affects transvascular passage and interstitial accumulation of charged molecules in both normal and pathological tissues. In the present study, we thereby developed an electrodiffusion-convection model to investigate the mechanisms by which the negatively charged tissue matrix regulates the interstitial transport of charged macromolecules. Our model predictions demonstrated that the tissue diffusion coefficient of negatively charged albumin (net charge = −19) in rat mesentery is comparable to that of neutral dextran with equivalent hydrodynamic radius. The discrepancy in their interstitial concentration profiles observed by Fox and Wayland (Microvasc. Res. 18:255–276, 1979) can be explained by the charge effect, specifically, by the electrical partition at the interface between the non-charged space at the vessel wall exit and the charged tissue space, instead of by different tissue diffusion coefficients that Fox and Wayland postulated. This charge effect induces equivalent to approximately two-fold difference in tissue diffusion coefficients of charged albumin and neutral dextran with the same free diffusion coefficients. Furthermore, our results indicate that increased filtration by increased microvessel permeability greatly enhances the accumulation of positively charged macromolecules in the interstitial space but not that of negatively charged ones.