Leakiness and Size Exclusion of Paracellular Channels in Cultured Epithelial Cell Monolayers-Interlaboratory Comparison

Purpose To determine and compare the paracellular characteristics of permeability (Papp) of Caco-2, MDCK, and 2/4/A1 cell lines. Methods The Papp data from 14 studies were analyzed by weighted nonlinear regression in terms of the paracellular parameters: porosity-pathlength (ε/δ), pore radius (R), and electrostatic potential drop (Δφ). Aqueous diffusivities, Daq, for the analysis, were empirically determined. The required hydrodynamic radii, rHYD, were estimated without knowledge of compound density. Mannitol iso-paracellular profiles allowed comparisons of “leakiness” across labs. Results Daq (37°C) was predicted as 9.9 × 10⁻⁵ MW⁻⁰.⁴⁵³; rHYD = (0.92 + 21.8 MW⁻¹)·rSE, where rSE is the Stokes-Einstein radius. Values of pore radius ranged from 4.0(±0.1) to 18(±3) Å, with the 2/4/A1 indicating the largest pores. The ε/δ capacity factor ranged from 0.2 (±0.1) to 69 (±5) cm⁻¹, with most values