The interaction of cells in a tissue depends on the nature of the extracellular matrix. The electrical properties of the narrow extracellular space are unknown. Here we consider cell adhesion mediated by extracellular matrix protein on a solid substrate as a model system. We culture HEK 293 cells on silica coated with fibronectin and determine the electrical resistivity in the cell-solid junction rhoJ=rJdJ by combining measurements of the sheet resistance rJ and of the distance dJ between membrane and substrate. The sheet resistance is obtained from phase fluorometry of the voltage-sensitive dye ANNINE-5 by ac stimulation from the substrate. The distance is measured by fluorescence interference contrast (FLIC) microscopy. We change the resistivity of the bath in a range from 66 Ohm*cm to 750 Ohm*cm and find that the sheet resistance rJ is proportionally enhanced, but that the distance is invariant around dJ=75 nm. In all cases, the resulting resistivity rhoJ is indistinguishable from the resistivity of the bath. A similar result is obtained for rat neurons cultured on polylysine. On that basis we propose a Bulk Resistivity In Cell Adhesion (BRICA) model for cell-solid junctions. The observations suggest that the electrical interaction between cells in a tissue is determined by an extracellular space with the electrical properties of bulk electrolyte.
Integral distribution of cell-chip distances and sheet resistances for HEK293 cells on fibronectin in physiological electrolyte and in high resistivity electrolyte. (a) Cell-chip distance dJ at a bath resistivity rhoE=68 Ohm*cm (n = 60) fitted with an average < dJ > = 74 nm and sigmad = 7 nm. (b) Cell-chip distance at a bath resistivity rhoE=745 Ohm*cm (n = 122) fitted with < dJ > = 76 nm and sigmad = 7 nm. (c) Extracellular sheet resistance rJ. The data (n = 9) at rhoE=66 Ohm*cm are fitted with an average < rJ > = 7.7 MOhm and with sigmar = 1.4 MOhm. The data (n = 14) at rhoE=745 Ohm*cm are fitted with < rJ > = 85 MOhm and sigmar = 17 MOhm.
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