Microvascular Permeability and Tumor Metastasis - Bioanalysis Advanced Materials Methods and Devices - page 57

4.3.3 Charge Effects of the Endothelial Surface Glycocalyx
Due to the composition of the ESG, it carries a negative charge [ 57 , 88 ] and it would
affect the permeability and selectivity of the microvessel wall to water and solutes.
Previously, a simple 1D Donnan-type model had been proposed to describe the
charge effect on microvessel permeability [ 57 ]. It was based on a Donnan equilib-
rium distribution of ions, which exists as a result of retention of negative charges on
the capillary membrane. Later, an electrochemical model was proposed by
Damiano and Stace [ 20 ] for the transport of charged molecules through the capil-
lary glycocalyx without considering transport through the cleft region. To investi-
gate the charge selectivity on microvessel permeability, Fu et al. [ 29 ] extended
the 3D junction-orifice-fiber matrix model developed by Fu et al. [ 28 ] for the
interendothelial cleft to include a negatively charged glycocalyx layer at the
entrance of the interendothelial cleft. Both electrostatic and steric exclusions on
charged solutes are considered at the interfaces of the glycocalyx layer between the
vessel lumen and between the endothelial cleft. The effect of electrostatic
interactions between charged solutes and the matrix on solute transport is also
described within the glycocalyx layer. Their model can successfully explain the
observations in [ 57 ]. Recently, an electrodiffusion-filtration model has been devel-
oped to describe the transport of negatively charged macromolecules, bovine
serum albumin, across venular microvessels in frog mesentery [ 15 ]. A very inter-
esting prediction is that the convective component of albumin transport is greatly
diminished by the presence of a negatively charged glycocalyx. Most recently, Li
and Fu [ 46 ] have developed a model for the charge effect of the ESG and the
basement membrane between the endothelium and astrocyte foot processes on the
transport across the blood-brain barrier.
Bhalla and Deen [ 9 ] studied the effects of charge on osmotic reflection
coefficients of macromolecules in porous membranes. Sugihara-Seki et al. [ 77 ]
proposed an electrostatic model to predict the effects of surface charge on the
osmotic reflection coefficient of charged spherical solute across the ESG, based on
the combination of low-Reynolds-number hydrodynamics and a continuum
description of the electric double layers. The ESG was assumed to consist of
identical circular cylinders with a fixed surface charge, aligned parallel to each
other so as to form an ordered hexagonal arrangement. Their model predicts that the
charge of the ESG contributes significantly to the microvessel reflection coefficient
to albumin, which was reported in Michel and Curry [ 57 ].
4.4 Microvascular Hyperpermeability and Tumor Metastasis
The danger of cancer is organ failure caused by metastatic tumors that are
derivedfrom the primary tumor [ 73 ]. One critical step in tumor metastasis is
adhesion of primary tumor cells to the endothelium forming the microvascular