Agarose-Dextran Gels as Synthetic Analogs of Glomerular Basement Membrane: Water Permeability

Abstract

Novel agarose–dextran hydrogels were synthesized and their suitability as experimental models of glomerular basement membrane was examined by measuring their Darcy (hydraulic) permeabilities ( κ). Immobilization of large dextran molecules in agarose was achieved by electron beam irradiation. Composite gels were made with agarose volume fractions ( ϕ a) of 0.04 or 0.08 and dextran volume fractions ( ϕ d) ranging from 0 to 0.02 (fiber volume/gel volume), using either of two dextran molecular weights (500 or 2000). At either agarose concentration and for either size of dextran, κ decreased markedly as the amount of dextran was increased. Statistically significant deviations from the value of κ for pure agarose were obtained for remarkably small volume fractions of dextran: ϕ d ≥ 0.0003 for ϕ a = 0.04 and ϕ d ≥ 0.001 for ϕ a = 0.08. The Darcy permeabilities were much more sensitive to ϕ d than to ϕ a, and were as much as 26 times smaller than those of pure agarose. Although ϕ d was an important variable, dextran molecular weight was not. The effects of dextran addition on κ were described fairly well using simple structural idealizations. At high agarose concentrations, the dextran chains behaved as fine fibers interspersed among coarse agarose fibrils, whereas, at low concentrations, the dextran molecules began to resemble spherical obstacles embedded in agarose gels. The ability to achieve physiologically relevant Darcy permeabilities with these materials (as low as 1.6 nm 2) makes them an attractive experimental model for glomerular basement membrane and possibly other extracellular matrices.