Molecular conformation and filtration properties of anionic Ficoll

Groszek, Joseph J.; Li, Lingyan; Ferrell, Nicholas; Smith, Ronan J.; Zorman, Christian A.; Hofmann, Christina L.; Roy, Shuvo; Fissell, William H.

doi:10.1152/ajprenal.00324.2010

Cited by 18 publications

(24 citation statements)

References 39 publications

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“…In the present study we found that the sieving coefficients for aFicoll Ն35 Å in radius (for approaching or exceeding 1) significantly deviated from those predicted by the charged fibermatrix model, in that sieving coefficients for aFicoll approached those for nFicoll. A similar phenomenon has been observed for aFicoll vs. nFicoll in artificial membranes (17). This may indicate that charge restriction effects tend to be markedly reduced in magnitude when the size of the charged molecules approaches the size of the transport limiting structures of the barrier or that charge selectivity is much more complex than predicted from a charged fiber-matrix model.…”

Section: Discussionsupporting

confidence: 70%

“…The electric charge of the aFicoll used in the experiments has been quantified in terms of the zeta potential (see Fig. 1), which is the electric potential at the slipping plane, with values of Ϫ40 mV and Ϫ45 mV for CM-Ficoll 70 and CM-Ficoll 400, respectively (17). The surface charge density can be approximated using the Grahame equation…”

Section: Theorymentioning

confidence: 99%

“…In contrast to these results, there are extensive experimental results from both synthetic membranes and the glomerulus that demonstrate that globular proteins are selected based both on their size and charge (19,34). Using anionic 5.8-and 20-nm (pore radius) silicon nanopore membranes, Fissell and colleagues (17) showed a charge-dependent permselectivity for aFicoll. Using the same charge-modification technique for CM-Ficoll, our own experiments have demonstrated a reduced transport of aFicoll relative to nFicoll across the rat GFB (4).…”

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confidence: 99%

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Quantification of the electrostatic properties of the glomerular filtration barrier modeled as a charged fiber matrix separating anionic from neutral Ficoll

Öberg

Rippe

2013

American Journal of Physiology-Renal Physiology

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Öberg CM, Rippe B. Quantification of the electrostatic properties of the glomerular filtration barrier modeled as a charged fiber matrix separating anionic from neutral Ficoll. Am J Physiol Renal Physiol 304: F781-F787, 2013. First published January 9, 2013 doi:10.1152/ajprenal.00621.2012.-In the current study we explore the electrostatic interactions on the transport of anionic Ficoll (aFicoll) vs. neutral Ficoll (nFicoll) over the glomerular filtration barrier (GFB) modeled as a charged fiber matrix. We first analyze experimental sieving data for the rat glomerulus, and second, we explore some of the basic implications of a theoretical model for the electrostatic interactions between a charged solute and a charged fiber-matrix barrier. To explain the measured difference in glomerular transport between nFicoll and aFicoll (Axelsson J, Sverrisson K, Rippe A, Fissell W, Rippe B. Am J Physiol 301: F708 -F712, 2011), the present simulations demonstrate that the surface charge density needed on a charged fiber matrix must lie between Ϫ0.005 C/m 2 and Ϫ0.019 C/m 2 , depending on the surface charge density of the solute. This is in good agreement with known surface charge densities for many proteins in the body. In conclusion, the current results suggest that electrical charge makes a moderate contribution to glomerular permeability, while molecular size and conformation seem to be more important. Yet, the weak electrical charge obtained in this study can be predicted to nearly totally exclude albumin from permeating through "high-selectivity" pathways in a charged-fiber matrix of the GFB. capillary permeability; fiber matrix; anionic Ficoll; charge selectivity THE RELATIVE IMPORTANCE OF electrical charge in the sieving of plasma proteins across the glomerular filtration barrier (GFB) has been a matter of debate over the last few decades. The seminal data of Brenner an colleagues (8, 10), using differently charged dextran thus suggested that the glomerular transport of negatively charged, sulfated dextran molecules be much lower than that of neutral dextran of the same size (8). However, several authors have questioned these results. Thus some fractions of sulfated dextran seem to bind to plasma proteins or glomerular cells (18,33). In addition, it has been shown that polysaccharides (such as dextran and Ficoll) exhibit a flexible molecular conformation, making them hyperpermeable compared with more rigid solutes, such as proteins, at least for molecular radii approaching the pore radius (1, 12). Ficoll apparently shows glomerular sieving characteristics somewhere between those of dextran and proteins (34). Several findings also suggest that polysaccharides undergo significant conformational changes during charge modification, making them even more flexible. Hence, Asgeirsson et al. (2) conducted an experiment investigating the glomerular sieving of carboxymethylated (CM) anionic Ficoll (aFicoll) and "unmodified" neutral Ficoll (nFicoll) in rats. The glomerular permeability to negatively charged CM-Ficoll was markedl...

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Section: Discussionsupporting

confidence: 70%

Section: Theorymentioning

confidence: 99%

mentioning

confidence: 99%

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Quantification of the electrostatic properties of the glomerular filtration barrier modeled as a charged fiber matrix separating anionic from neutral Ficoll

Öberg

Rippe

2013

American Journal of Physiology-Renal Physiology

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“…The authors suggested that the observed hyperpermeability, both in vivo and in vitro, in Ficoll solutions is unlikely to originate from shear-induced conformational changes. In systematic studies of the larger branched polymer Ficoll PM400 bimodal distributions were observed in size exclusion chromatography experiments (SEC) [2,29]. The findings suggest that Ficoll PM400 may contain two distinct size distributions, although the lower molecular mass material could not be resolved.…”

Section: Discussionmentioning

confidence: 99%

Light scattering studies on Ficoll PM70 solutions reveal two distinct diffusive modes

Georgalis

Philipp

Aleksandrova

et al. 2012

Journal of Colloid and Interface Science

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“…The basis for the apparently paradoxical effect was attributed either to an absence of electrostatic hindrance or to conformational differences between neutral and anionic Ficoll (2,25). To probe this question more deeply, our group developed an anionic Ficoll that appeared to be conformationally similar to neutral Ficoll and was retarded by anionic membranes (24). Having completed some very preliminary studies on solute partitioning by extracellular matrices, we sought evidence to support either enhanced or retarded transmission of anionic polysaccharides through a model of the GBM.…”

mentioning

confidence: 99%

Basal lamina secreted by MDCK cells has size- and charge-selective properties

Ferrell

Groszek

et al. 2011

American Journal of Physiology-Renal Physiology

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The role electrical charge plays in determining glomerular permeability to macromolecules remains unclear. If the glomerular basement membrane (GBM) has any significant role in permselectivity, physical principles would suggest a negatively charged GBM would reject similarly charged more than neutral species. However, recent in vivo studies with negative and neutral glomerular probes showed the opposite. Whether this observation is due to unique characteristics of the probes used or is a general physiological phenomenon remains to be seen. The goal of this study was to use the basement membrane deposited by Madin-Darby canine kidney epithelial cells as a simple model of a biologically derived, negatively charged filter to evaluate size- and charge-based sieving properties. Fluorescein isothiocyanate-labeled carboxymethylated Ficoll 400 (FITC-CM Ficoll 400) and amino-4-methyl-coumarin-labeled Ficoll 400 (AMC Ficoll 400) were used as negatively charged and neutral tracer molecules, respectively, during pressure-driven filtration. Streaming potential measurement indicated the presence of fixed, negative charge in the basal lamina. The sieving coefficient for neutral Ficoll 400 decreased by ∼0.0013 for each 1-Å increment in solute radius, compared with a decrease of 0.0023 per Å for the anionic Ficoll 400. In this system, molecular charge played a significant role in determining the sieving characteristics of the membrane, pointing to solute charge as a potential contributor to GBM permselectivity.

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Molecular conformation and filtration properties of anionic Ficoll

Cited by 18 publications

References 39 publications

Quantification of the electrostatic properties of the glomerular filtration barrier modeled as a charged fiber matrix separating anionic from neutral Ficoll

Quantification of the electrostatic properties of the glomerular filtration barrier modeled as a charged fiber matrix separating anionic from neutral Ficoll

Light scattering studies on Ficoll PM70 solutions reveal two distinct diffusive modes

Basal lamina secreted by MDCK cells has size- and charge-selective properties

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