Biomimetic artificial cells to model the effect of membrane asymmetry on chemoresistance

Abstract

We present a microfluidic platform that enables the formation of bespoke asymmetric droplet interface bilayers (DIBs) as artificial cell models from naturally-derived lipids. We use them to perform pharmacokinetic assays to quantify how lipid asymmetry affects the permeability of the chemotherapy drug doxorubicin. Previous attempts to model bilayer asymmetry with DIBs have relied on the use of synthetic lipids to achieve asymmetry. Use of natural lipids serves to increase the biomimetic nature of these artificial cells, showcasing the next step towards forming a true artificial cell membrane in vitro. Here we use our microfluidic platform to form biomimetic, asymmetric and symmetric DIBs, with their asymmetry quantified through their life-mimicking degree of curvature. We subsequently examine permeability of these membranes to doxorubicin, and reveal measurable differences in its pharmacokinetics induced by membrane asymmetry, highlighting another factor that potentially contributes to chemoresistance in some forms of cancer.