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A distributed solute model : An extended two-pore model with application to the glomerular sieving of ficoll

Öberg, Carl M. LU ; Groszek, Joseph J.; Roy, Shuvo; Fissell, William H. and Rippe, Bengt LU (2018) In American Journal of Physiology - Renal Physiology 314(6). p.1108-1116
Abstract

One of the many unresolved questions regarding the permeability of the glomerular filtration barrier is the reason behind the marked difference in permeability between albumin and polysaccharide probe molecules such as Ficoll and dextran of the same molecular size. Although the differences in permeability have been mainly attributed to charge effects, we have previously shown that this would require a highly charged filtration barrier, having a charge density that is ~10 times more than that on the albumin molecule. In this article, the classic two-pore model was extended by introducing size distributions on the solute molecules, making them conformationally flexible. Experimental sieving data for Ficoll from the rat glomerulus and from... (More)

One of the many unresolved questions regarding the permeability of the glomerular filtration barrier is the reason behind the marked difference in permeability between albumin and polysaccharide probe molecules such as Ficoll and dextran of the same molecular size. Although the differences in permeability have been mainly attributed to charge effects, we have previously shown that this would require a highly charged filtration barrier, having a charge density that is ~10 times more than that on the albumin molecule. In this article, the classic two-pore model was extended by introducing size distributions on the solute molecules, making them conformationally flexible. Experimental sieving data for Ficoll from the rat glomerulus and from precision-made silicon nanopore membranes were analyzed using the model. For the rat glomerulus a small-pore radius of 36.2 Å and a geometric standard deviation (gSD) for the Ficoll size-distribu-tion of 1.16 were obtained. For the nanopore membranes, a gSD of 1.24 and a small-pore radius of 43 Å were found. Interestingly, a variation of only ~16% in the size of the polysaccharide molecule is sufficient to explain the difference in permeability between albumin and Ficoll. Also, in line with previous data, the effects of applying a size distribution on the solute molecule are only evident when the molecular size is close to the pore size. Surely there is at least some variation in the pore radii, and, likely, the gSD obtained in the current study is an overestimation of the “true” variation in the size of the Ficoll molecule.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Heteroporous model, Pore model, Sieving coefficient
in
American Journal of Physiology - Renal Physiology
volume
314
issue
6
pages
1108 - 1116
publisher
American Physiological Society
external identifiers
  • scopus:85047948349
ISSN
0363-6127
DOI
10.1152/ajprenal.00066.2017
language
English
LU publication?
yes
id
b0857f8d-ebbc-4862-b54e-6a5c5c567c1d
date added to LUP
2018-06-11 13:03:24
date last changed
2018-06-12 03:00:03
@article{b0857f8d-ebbc-4862-b54e-6a5c5c567c1d,
  abstract     = {<p>One of the many unresolved questions regarding the permeability of the glomerular filtration barrier is the reason behind the marked difference in permeability between albumin and polysaccharide probe molecules such as Ficoll and dextran of the same molecular size. Although the differences in permeability have been mainly attributed to charge effects, we have previously shown that this would require a highly charged filtration barrier, having a charge density that is ~10 times more than that on the albumin molecule. In this article, the classic two-pore model was extended by introducing size distributions on the solute molecules, making them conformationally flexible. Experimental sieving data for Ficoll from the rat glomerulus and from precision-made silicon nanopore membranes were analyzed using the model. For the rat glomerulus a small-pore radius of 36.2 Å and a geometric standard deviation (gSD) for the Ficoll size-distribu-tion of 1.16 were obtained. For the nanopore membranes, a gSD of 1.24 and a small-pore radius of 43 Å were found. Interestingly, a variation of only ~16% in the size of the polysaccharide molecule is sufficient to explain the difference in permeability between albumin and Ficoll. Also, in line with previous data, the effects of applying a size distribution on the solute molecule are only evident when the molecular size is close to the pore size. Surely there is at least some variation in the pore radii, and, likely, the gSD obtained in the current study is an overestimation of the “true” variation in the size of the Ficoll molecule.</p>},
  author       = {Öberg, Carl M. and Groszek, Joseph J. and Roy, Shuvo and Fissell, William H. and Rippe, Bengt},
  issn         = {0363-6127},
  keyword      = {Heteroporous model,Pore model,Sieving coefficient},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1108--1116},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Renal Physiology},
  title        = {A distributed solute model : An extended two-pore model with application to the glomerular sieving of ficoll},
  url          = {http://dx.doi.org/10.1152/ajprenal.00066.2017},
  volume       = {314},
  year         = {2018},
}