A three-dimensional junction-pore-matrix model for capillary permeability

Weinbaum, Sheldon; Tsay, Ruey Yug; Curry, F. E.

doi:10.1016/0026-2862(92)90104-w

Cited by 72 publications

(71 citation statements)

References 24 publications

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“…Applying mathematical and biophysical models, the contribution of each component can be inferred but to date cannot be measured directly as has been done with the GBM (36). In fact, mathematical models have attempted to explain permselectivity, but the tools to validate these hypotheses are lacking (37,38). This cultured podocyte cell line provides the first opportunity to define characteristics that are unique to podocytes in the absence of other components, such as the endothelium and GBM.…”

Section: Discussionmentioning

confidence: 99%

Cultured Podocytes Establish a Size-Selective Barrier Regulated by Specific Signaling Pathways and Demonstrate Synchronized Barrier Assembly in a Calcium Switch Model of Junction Formation

Hunt

Pollak

Denker

2005

Journal of the American Society of Nephrology

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Podocytes form unique cell-cell junctions (slit diaphragms) that are central to glomerular selectivity, although regulation and mechanisms of slit diaphragm assembly are poorly understood. With the use of cultured podocytes, a paracellular permeability flux assay was established to characterize properties of the size-selective barrier. Paracellular flux of differentiated podocytes was measured using anionic fluorescent dextrans of 3, 10, 40, and 70 kD. Podocytes form a highly selective barrier with a 160-fold difference in flux from the 3-kD dextran (11 pmol/min) to the 70-kD dextran (0.06 pmol/min). Barrier development was dependent on podocyte differentiation and not affected by dextran charge. Puromycin, a known podocyte toxin, increased flux 250% in a dose-dependent manner without affecting cell viability. Screening with modulators of specific signaling pathways identified reversible increases in flux with Src tyrosine and Rho kinase inhibition. The calcium switch model of epithelial junction assembly was modified to determine whether podocytes regulate barrier assembly. When cultured in low calcium for 90 min, flux increased by 300% and consistently returned to baseline 24 to 48 h after switching to normal calcium. Similar to classical epithelial junctions, barrier recovery occurred in the presence of cyclohexamide, an inhibitor of protein synthesis. During the calcium switch, there were reversible changes in localization and detergent solubility of the slit diaphragm protein ZO-1 and ␣-actinin-4, whereas nephrin and podocin solubility were unchanged. Taken together, these findings demonstrate that cultured podocytes develop a selective size barrier that is regulated by specific signaling pathways, and similar to classical epithelial junctions, podocytes demonstrate synchronized assembly of the barrier.

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Section: Discussionmentioning

confidence: 99%

Cultured Podocytes Establish a Size-Selective Barrier Regulated by Specific Signaling Pathways and Demonstrate Synchronized Barrier Assembly in a Calcium Switch Model of Junction Formation

Hunt

Pollak

Denker

2005

Journal of the American Society of Nephrology

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“…We used fiber radius a ϭ 0.6 nm and gap spacing ⌬ ϭ 7 nm if periodic fiber arrays exist or volume fraction of fiber matrix S f ϭ 0.11 if random fiber arrays exist. The values of ⌬ or S f lead to a diffusion coefficient of a solute with radius rs ϭ 2.01 nm in the fiber matrix of Di,f ϭ 0.025 ϫ 10 Ϫ6 cm 2 /s (13,22). Properties of ions and charged solutes.…”

Section: Parameter Valuesmentioning

confidence: 99%

“…On the tissue side of the fiber layer at the cleft entrance, we assumed a negligible concentration of proteins because the fiber layer behaves as the molecular filter to proteins (22). To satisfy the electrical neutrality, C ϩ should be identical to CϪ on the tissue side of the fiber layer, whose values are dependent on Cϩ and CϪ in the lumen as well as the charge density of the surface glycocalyx at the interface of the cleft entrance.…”

Section: Parameter Valuesmentioning

confidence: 99%

“…Although this model described the steric and electrostatic partition to a charged solute at the interface between the membrane and the solution, it neglected the thickness of the membrane and thus neglected the steric and electrostatic interactions between the solutes and the membrane components within the membrane. A more sophisticated model for steric and diffusion resistance to solute transport in the fiber matrix was proposed by Weinbaum et al (22). With the use of this theory for the entrance fiber layer, Fu et al (10)(11)(12)(13) developed a three-dimensional model for the interendothelial cleft to describe solute exchange across the microvessel.…”

mentioning

confidence: 99%

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An electrodiffusion model for effects of surface glycocalyx layer on microvessel permeability

Chen²,

Chen³

2003

American Journal of Physiology-Heart and Circulatory Physiology

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To investigate the charge effect of the endothelial surface glycocalyx on microvessel permeability, we extended the three-dimensional model developed by Fu et al. (J Biomech Eng 116: 502-513, 1994) for the interendothelial cleft to include a negatively charged glycocalyx layer at the entrance of the cleft. Both electrostatic and steric exclusions on charged solutes were considered within the glycocalyx layer and at the interfaces. Four chargedensity profiles were assumed for the glycocalyx layer. Our model indicates that the overall solute permeability across the microvessel wall including the surface glycocalyx layer and the cleft region is independent of the charge-density profiles as long as they have the same maximum value and the same total charge. On the basis of experimental data, this model predicts that the charge density would be 25-35 meq/l in the glycolcalyx of frog mesenteric capillaries. An intriguing prediction of this model is that when the concentrations of cations and anions are unequal in the lumen due to the presence of negatively charged proteins, the negatively charged glycocalyx would provide more resistance to positively charged solutes than to negatively charged ones. model for charge effect of endothelial surface glycocalyx; microvessel permeability to charged molecules; interendothelial cleft

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“…Glycocalyx can be considered as a hydrogel layer with negative charges, because it is a negatively charged macromolecules composed of glycoproteins and proteoglycans [11,12] whose polymer volume fraction has been theoretically estimated to be 1%  2% [31,32]. We assume that the glycocalyx is crucial for the surface friction of the EC monolayer.…”

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confidence: 99%

Study on the Sliding Friction of Endothelial Cells Cultured on Hydrogel and the Role of Glycocalyx on Friction Reduction

et al. 2010

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In this study, we investigated the sliding friction of human umbilical vein endothelial cell (HUVEC) monolayer cultured on poly(sodium p-styrene sulfonate) (PNaSS) gel, intending to elucidate the role of the glycocalyx on the surface of endothelial cell (EC) in friction reduction.Three sets of HUVEC monolayers were investigated: 1) as-cultured HUVEC monolayer, 2) HUVEC monolayer treated by transforming growth factor  1 (TGF- 1 ), which increased glycocalyx by 148%, 3) HUVEC monolayer treated by heparinase I, which reduced glycocalyx by 57%, both were compared with that of the as prepared one. When being slid on flat glass surface, the frictional stress of HUVEC monolayer decreased in the order of heparinase I-treated > as-cultured > TGF- 1 -treated samples. The results suggested that glycocalyx may play a role in reducing the friction of endothelial cell monolayer.

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A three-dimensional junction-pore-matrix model for capillary permeability

Cited by 72 publications

References 24 publications

Cultured Podocytes Establish a Size-Selective Barrier Regulated by Specific Signaling Pathways and Demonstrate Synchronized Barrier Assembly in a Calcium Switch Model of Junction Formation

Cultured Podocytes Establish a Size-Selective Barrier Regulated by Specific Signaling Pathways and Demonstrate Synchronized Barrier Assembly in a Calcium Switch Model of Junction Formation

An electrodiffusion model for effects of surface glycocalyx layer on microvessel permeability

Study on the Sliding Friction of Endothelial Cells Cultured on Hydrogel and the Role of Glycocalyx on Friction Reduction

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