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Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability.

Venturoli, Daniele LU and Rippe, Bengt LU (2005) In American Journal of Physiology: Renal, Fluid and Electrolyte Physiology 288(4). p.605-613
Abstract
Polydisperse mixtures of dextran or Ficoll have been frequently used as molecular probes for studies of glomerular permselectivity because they are largely inert and not processed (reabsorbed) by the proximal tubules. However, dextrans are linear, flexible molecules, which apparently are hyperpermeable across the glomerular barrier. By contrast, the Ficoll molecule is almost spherical. Still, there is ample evidence that Ficoll fractional clearances (sieving coefficients) across the glomerular capillary wall (GCW) are markedly higher than those for neutral globular proteins of an equivalent in vitro Stokes-Einstein (SE) radius. Physical data, obtained by "crowding" experiments or measurements of intrinsic viscosity, suggest that the Ficoll... (More)
Polydisperse mixtures of dextran or Ficoll have been frequently used as molecular probes for studies of glomerular permselectivity because they are largely inert and not processed (reabsorbed) by the proximal tubules. However, dextrans are linear, flexible molecules, which apparently are hyperpermeable across the glomerular barrier. By contrast, the Ficoll molecule is almost spherical. Still, there is ample evidence that Ficoll fractional clearances (sieving coefficients) across the glomerular capillary wall (GCW) are markedly higher than those for neutral globular proteins of an equivalent in vitro Stokes-Einstein (SE) radius. Physical data, obtained by "crowding" experiments or measurements of intrinsic viscosity, suggest that the Ficoll molecule exhibits a rather open, deformable structure and thus deviates from an ideally hard sphere. This is also indicated from the relationship between (log) in vitro SE radius and (log) molecular weight (MW). Whereas globular proteins seem to behave in a way similar to hydrated hard spheres, polydisperse dextran and Ficoll exhibit in vitro SE radii that are much larger than those for compact spherical molecules of equivalent MW. For dextran, this can be partially explained by a high-molecular-size asymmetry. However, for Ficoll the explanation may be that the Ficoll molecule is more flexible (deformable) than are globular proteins. An increased compressibility of Ficoll and an increased deformability and size asymmetry for dextran may be the explanation for the fact that the permeability of the GCW is significantly higher when assessed using polysaccharides such as Ficoll or dextran compared with that obtained using globular proteins as molecular size probes. We suggest that molecular deformability, besides molecular size, shape, and charge, plays a crucial role in determining the glomerular permeability to molecules of different species. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
macromolecules, reflection coefficient, transport, polysaccharides, capillary permeability
in
American Journal of Physiology: Renal, Fluid and Electrolyte Physiology
volume
288
issue
4
pages
605 - 613
publisher
American Physiological Society
external identifiers
  • wos:000227495000001
  • pmid:15753324
  • scopus:15044362503
ISSN
0363-6127
DOI
10.1152/ajprenal.00171.2004
language
English
LU publication?
yes
id
45ffdbf6-12f3-4821-a9fa-455feb532db2 (old id 135143)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15753324&dopt=Abstract
date added to LUP
2007-07-25 08:58:12
date last changed
2017-11-19 03:26:34
@article{45ffdbf6-12f3-4821-a9fa-455feb532db2,
  abstract     = {Polydisperse mixtures of dextran or Ficoll have been frequently used as molecular probes for studies of glomerular permselectivity because they are largely inert and not processed (reabsorbed) by the proximal tubules. However, dextrans are linear, flexible molecules, which apparently are hyperpermeable across the glomerular barrier. By contrast, the Ficoll molecule is almost spherical. Still, there is ample evidence that Ficoll fractional clearances (sieving coefficients) across the glomerular capillary wall (GCW) are markedly higher than those for neutral globular proteins of an equivalent in vitro Stokes-Einstein (SE) radius. Physical data, obtained by "crowding" experiments or measurements of intrinsic viscosity, suggest that the Ficoll molecule exhibits a rather open, deformable structure and thus deviates from an ideally hard sphere. This is also indicated from the relationship between (log) in vitro SE radius and (log) molecular weight (MW). Whereas globular proteins seem to behave in a way similar to hydrated hard spheres, polydisperse dextran and Ficoll exhibit in vitro SE radii that are much larger than those for compact spherical molecules of equivalent MW. For dextran, this can be partially explained by a high-molecular-size asymmetry. However, for Ficoll the explanation may be that the Ficoll molecule is more flexible (deformable) than are globular proteins. An increased compressibility of Ficoll and an increased deformability and size asymmetry for dextran may be the explanation for the fact that the permeability of the GCW is significantly higher when assessed using polysaccharides such as Ficoll or dextran compared with that obtained using globular proteins as molecular size probes. We suggest that molecular deformability, besides molecular size, shape, and charge, plays a crucial role in determining the glomerular permeability to molecules of different species.},
  author       = {Venturoli, Daniele and Rippe, Bengt},
  issn         = {0363-6127},
  keyword      = {macromolecules,reflection coefficient,transport,polysaccharides,capillary permeability},
  language     = {eng},
  number       = {4},
  pages        = {605--613},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Renal, Fluid and Electrolyte Physiology},
  title        = {Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability.},
  url          = {http://dx.doi.org/10.1152/ajprenal.00171.2004},
  volume       = {288},
  year         = {2005},
}