Partitioning and diffusion of large molecules in fibrous structures

Bosma, J. C.; Wesselingh, J.A.

doi:10.1016/s0378-4347(00)00134-1

Cited by 61 publications

(87 citation statements)

References 19 publications

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“…8,9, and 11) both yielded slopes that were too large. The results obtained with two other models for diffusion in gels (Amsden, 1998;Bosma et al, 2000) generally gave larger mean square errors when applied to our agarose data than did those shown in Figure 3; those curves have been omitted for clarity. Thus, none of the available theories precisely captures the behavior of macromolecular diffusivities in pure agarose.…”

Section: Discussionmentioning

confidence: 66%

Diffusivities of macromolecules in composite hydrogels

Kosto

Deen

2004

AIChE Journal

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Section: Discussionmentioning

confidence: 66%

Diffusivities of macromolecules in composite hydrogels

Kosto

Deen

2004

AIChE Journal

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“…Ogston's equation for the fractional available volume in gels has survived many experimental tests of its validity (9,10) and has been rederived in other ways and has been somewhat modified (10,11). It still remains the simplest equation that predicts reasonably well the relationship between the sizes of macromolecules and the space available to them in gels of differing concentration and composition.…”

Section: Gbm Size Selectivitymentioning

confidence: 99%

Why the kidney glomerulus does not clog: A gel permeation/diffusion hypothesis of renal function

Smithies

2003

Proc. Natl. Acad. Sci. U.S.A.

138

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Current interpretations of kidney function in terms of a coarse filter followed by a fine filter have difficulty explaining why the glomerulus does not clog. I propose, as an alternative, a semiquantitative hypothesis that assumes that the size-selective property of the glomerulus is a consequence of the limited fraction of space in the glomerular basement membrane (a concentrated gel) into which macromolecules can permeate. The glomerular epithelial cell slits and slit diaphragms are assumed to impose substantial resistance to liquid flow across the glomerulus without acting as a molecular sieve. Calculations based on gel behavior show that proteins cross the glomerular basement membrane mainly by diffusion rather than by liquid flow, whereas water crosses entirely by flow. Thus, diffusion provides most of the protein, whereas flow provides the diluent. As a result, the single-nephron glomerular filtration rate (GFR) becomes a prime factor in (inversely) determining the concentration of proteins in early proximal tubular fluid. Because the reabsorption of proteins from the tubules is a saturable process, the gel permeation͞diffusion hypothesis readily accounts for the albuminuria observed when singlenephron GFR is substantially reduced by severe pathological decreases in slit diaphragm length, such as occur in minimal-change nephrotic syndrome in humans, in animals treated with puromycin aminonucleoside, or in humans or animals with mutations in the gene coding for nephrin. My hypothesis predicts that albuminuria will ensue, even with a normal kidney, if the single-nephron GFR falls below Ϸ50% of normal.H ow kidney glomeruli separate the macromolecular components of blood from small solutes has been debated for over 150 years (1, 2). The predominant current view, proposed in the 1960s by Karnovsky and Ainsworth (3), is that the glomerular basement membrane (GBM in Fig. 1) is a relatively coarse first stage filter and the slit diaphragm (SD in Fig. 1) is a second-stage molecular sieve with most pores being smaller than albumin. This view raises the question: Why doesn't it clog? In the following I provide an answer in the form of a semiquantitative gel permeation͞diffusion hypothesis of renal function. Although many of the ideas that I discuss have been considered individually by others, their integration in this manner has not, to my knowledge, been described.My permeation͞diffusion hypothesis depends on two main assumptions: (i) that the GBM is a gel (4) having size-selective properties determined by permeation (5) and diffusion (6), not by filtration; and (ii) that the slit diaphragm is essential for normal glomerular structure but does not act as a molecular sieve, even though it introduces considerable resistance to hydrodynamic flow (7). No special assumptions are then required to explain either the absence of clogging or the behavior of albumin. I present calculations showing that diffusion plays a greater role in the transport of macromolecules across the GBM gel than does liquid flow. This conclusion le...

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“…The diffusivities of the ions into the solid particle, Ð iM , are estimated using the Ogston model (Bosma and Wesselingh, 2000 where r i is the radius of the ion and f is the solid volume fraction in the demineralized layer. The radius of the collagen fibers, r f , is about 0.45 nm (Rose, 1980).…”

Section: Mass Transfer Described By Maxwell-stefan Modelmentioning

confidence: 99%