title: Contributions of fluid convection and electrical migration to transport in cartilage: relevance to loading.
abstract: We have studied the contributions of diffusion, fluid flow and electrical migration to molecular transport through adult articular cartilage explants using neutral and charged solutes that were either radiolabeled (3H2O, [35S]sulfate, [3H]thymidine, [3H]raffinose, and a synthetic matrix metalloproteinase inhibitor) or fluorescently tagged (NSPA and Lissamine-dextran). In order to induce fluid flow within the cartilage matrix without mechanical deformation, electric current densities were applied across cartilage disks. These currents produced electroosmotic fluid velocities of 1-2 microns/s, magnitudes that have been reported to exist during joint loading in vivo. This fluid convection enhanced neutral solute flux relative to passive diffusion alone by a factor that increased with the size of the solute. While the enhancement factor for 3H2O was 2.3-fold, that for [3H]raffinose (594 Da) and similar sized neutral solutes was 10-fold, suggesting that the effect of fluid flow is important even for small solutes. The largest enhancement (25-fold) was seen for the neutral 10-kDa Lissamine-dextran, confirming that fluid convection is most important for large solutes. We also studied the electrophoretic contribution to solute flux, which is relevant to the presence of intratissue streaming potentials induced during loading in vivo. Using the negatively charged [35S]sulfate ion with a range of current densities, as much as a 10-fold enhancement in flux was observed. Values for the intrinsic transport properties of the solutes (e.g., diffusivity, electrical mobility, hydrodynamic hindrance factor) can be obtained from the data.
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Garcia
authors.forename: E H
authors.initials: EH
authors.lastname: Frank
authors.forename: P E
authors.initials: PE
authors.lastname: Grimshaw
authors.forename: A J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D000818:Animals; D001692:Biological Transport; D002358:Cartilage, Articular / Q000502:physiology*; D002417:Cattle; D004058:Diffusion; D004151:Dipeptides / Q000378:metabolism; D004594:Electrophysiology; D005456:Fluorescent Dyes; D007700:Kinetics; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008954:Models, Biological; D009919:Orchiectomy; D009924:Organ Culture Techniques / Q000295:instrumentation / Q000379:methods; D009995:Osmosis; D011480:Protease Inhibitors / Q000378:metabolism; D011887:Raffinose / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014867:Water
chemical_list: D004151:Dipeptides; D005456:Fluorescent Dyes; D011480:Protease Inhibitors; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014867:Water; D014316:Tritium; C085083:N-(1-carboxyethyl)-alpha-(2-phenylethyl)glycyl-leucine, N-phenylamide; D008666:Metalloendopeptidases; D011887:Raffinose; D013936:Thymidine