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A Rapid, Scalable Method for the Isolation, Functional Study, and Analysis of Cell-derived Extracellular Matrix
Published on: January 4, 2017
Solute partitioning and filtration by extracellular matrices
William H Fissell1, Christina L Hofmann, Nicholas Ferrell
1Biomedical Engineering/ND20, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA. fisselw@ccf.org
American Journal of Physiology. Renal Physiology
|July 10, 2009
Summary
The glomerular basement membrane (GBM) may play a key role in protein retention during kidney filtration. Gel compression under pressure alters how the GBM filters macromolecules, potentially linking podocyte structure to filtration properties.
Area of Science:
- Nephrology
- Biophysics
- Materials Science
Background:
- Glomerular filtration physiology is not fully understood, despite its role in kidney disease.
- Podocytes are implicated as the filtration barrier, but macromolecule accumulation suggests otherwise.
- Macromolecule concentration gradients suggest the glomerular basement membrane (GBM) may act as the filter.
Purpose of the Study:
- To investigate the GBM's role in protein retention.
- To study the physical properties of model gels, including laminin-rich extracellular matrix (Matrigel) and lens basement membrane (LBM).
Main Methods:
- Experimental measurement of solute partitioning and filtration using Ficoll 70 tracer molecule in Matrigel and LBM.
- Numerical simulation of a novel laminin gel model and a mixed structure-random-fiber model for LBM.
- Analysis of size and flux dependence of sieving coefficients through Matrigel.
Main Results:
- Experimental partitioning data were accurately predicted by numerical simulations.
- Sieving coefficients for Matrigel were dependent on both solute size and filtration flux.
- Observed flux dependence was attributed to gel compression under applied pressure.
Conclusions:
- Gel compression in response to pressure may alter extracellular matrix solute partitioning at physiological pressures.
- This suggests a physical mechanism connecting podocyte structure to GBM permeability.
- The GBM's mechanical properties could be crucial in regulating kidney filtration and protein handling.
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