Challenges and opportunities in achieving the full potential of droplet interface bilayers.

Model membranes can be used to elucidate the intricacies of the chemical processes that occur in cell membranes, but the perfectly biomimetic, yet bespoke, model membrane has yet to be built. Droplet interface bilayers are a new type of model membrane able to mimic some features of real cell membranes better than traditional models, such as liposomes and black lipid membranes. In this Perspective, we discuss recent work in the field that is starting to showcase the potential of these model membranes to enable the quantification of membrane processes, such as the behaviour of protein transporters and the prediction of in vivo drug movement, and their use as scaffolds for electrophysiological measurements. We also highlight the challenges that remain to enable droplet interface bilayers to achieve their full potential as artificial cells, and as biological analytical platforms to quantify molecular transport.

Investigating the effect of phospholipids on droplet formation and surface property evolution in microfluidic devices for droplet interface bilayer (DIB) formation.

Despite growing interest in droplet microfluidic methods for droplet interface bilayer (DIB) formation, there is a dearth of information regarding how phospholipids impact device function. Limited characterization has been carried out for phospholipids, either computationally (in silico) or experimentally (in situ) in polydimethylsiloxane (PDMS) microfluidic devices, despite recent work providing a better understanding of how other surfactants behave in microfluidic systems. Hence, microfluidic device design for DIB applications relies heavily on trial and error, with many assumptions made about the impact of phospholipids on droplet formation and surface properties. Here, we examine the effects of phospholipids on interfacial tension, droplet formation, wetting, and hence device longevity, using DPhPC as the most widely used lipid for DIB formation. We use a customized COMSOL in silico model in comparison with in situ experimental data to establish that the stabilization of droplet formation seen when the lipid is dosed in the aqueous phase (lipid-in) or in the oil phase (lipid-out) is directly dependent on the effects of lipids on the device surface properties, rather than on how fast they coat the droplet. Furthermore, we establish a means to visually characterize surface property evolution in the presence of lipids and explore rates of device failure in the absence of lipid, lipid-out, and lipid-in. This first exploration of the effects of lipids on device function may serve to inform the design of microfluidic devices for DIB formation as well as to troubleshoot causes of device failure during microfluidic DIB experiments.

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

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.

Correction: A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes.

Correction for 'A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes' by Jaime L. Korner et al., Lab Chip, 2020, 20, 1898-1906, DOI: 10.1039/D0LC00263A.

A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes.

Early prediction of the rate and extent of intestinal absorption is vital for the efficient development of orally administered drugs. Here we show a new type of pharmacokinetic compartment model that shows a threefold improvement in the prediction of molecular absorption in the jejunum than the current state-of-the-art in vitro technique, parallel artificial membrane permeability assays (PAMPA). Our three-stage pharmacokinetic compartment model uses microfluidic droplets and bespoke, biomimetic artificial cells to model the path of a drug proxy from the intestinal space into the blood via an enterocyte. Each droplet models the buffer and salt composition of each pharmacokinetic compartment. The artificial cell membranes are made from the major components of human intestinal cell membranes (l-α-phosphatidylcholine, PC and l-α-phosphatidylethanolamine, PE) and sizes are comparable to human cells (∼0.5 nL). We demonstrate the use of the microfluidic platform to quantify common pharmacokinetic parameters such as half-life, flux and the apparent permeability coefficient (Papp). Our determined Papp more closely resembles that of actual intestinal tissue than PAMPA, which overestimates it by a factor of 20.