Active transport across biological membranes : quantification and limits

Abstract

Caco-2/MDCK assays are key tools for assessing compound permeability and active transport. The efflux ratio (ER) is often used to infer active efflux, but cannot be used as a direct measure of active transport. This work probes the viability of using intrinsic values to quantify efflux by extending existing models to incorporate aqueous boundary layers (ABL) and paracellular transport. It was found that the ABL does not affect the ER, but paracellular transport does. Evidence is also presented for a basolateral influx transporter. Finally, the study proposes a membrane permeability threshold beyond which active efflux is energetically implausible. Analysis of literature data supports this threshold, and a maximal active efflux flux value is determined empirically. These findings enable the prediction of non-effluxed compounds based on permeability alone, reducing the reliance on in vitro assays.