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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/F1092    most recent 00162.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Fissell, W. H. Articles by Roy, S. PubMed PubMed Citation Articles by Fissell, W. H. Articles by Roy, S.

Solute partitioning and filtration by extracellular matrices

Departments of ¹Nephrology and Hypertension and ; ²Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio; ; ³Department of Chemical Engineering, Pennsylvania State University, University Park, Pennsylvania; and ; ⁴Department of Pathology and Laboratory Medicine, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey

Submitted March 18, 2009 ; accepted in final form July 1, 2009

The physiology of glomerular filtration remains mechanistically obscure despite its importance in disease. The correspondence between proteinuria and foot process effacement suggests podocytes as the locus of the filtration barrier. If so, retained macromolecules ought to accumulate at the filtration barrier, an effect called concentration polarization. Literature data indicate macromolecule concentrations decrease from subendothelial to subepithelial glomerular basement membrane (GBM), as would be expected if the GBM were itself the filter. The objective of this study was to obtain insights into the possible role of the GBM in protein retention by performing fundamental experimental and theoretical studies on the properties of three model gels. Solute partitioning and filtration through thin gels of a commercially available laminin-rich extracellular matrix, Matrigel, were measured using a polydisperse polysaccharide tracer molecule, Ficoll 70. Solute partitioning into laminin gels and lens basement membrane (LBM) were measured using Ficoll 70. A novel model of a laminin gel was numerically simulated, as well as a mixed structure-random-fiber model for LBM. Experimental partitioning was predicted by numerical simulations. Sieving coefficients through thin gels of Matrigel were size dependent and strongly flux dependent. The observed flux dependence arose from compression of the gel in response to the applied pressure. Gel compression may alter solute partitioning into extracellular matrix at physiologic pressures present in the glomerular capillary. This suggests a physical mechanism coupling podocyte structure to permeability characteristics of the GBM.

glomerulus; basement membranes; numerical modeling