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1.
Nat Chem ; 14(8): 862-870, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35879442

RESUMEN

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.


Asunto(s)
Membrana Dobles de Lípidos , Liposomas , Transporte Biológico , Membrana Celular , Membrana Dobles de Lípidos/química , Liposomas/química
2.
Soft Matter ; 17(39): 8891-8901, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34543370

RESUMEN

Droplet interface bilayers (DIBs) have recently started to be used as human-mimetic artificial cell membranes. DIBs are bilayer sections created at the interface of two aqueous droplets, such that one droplet can be used as a donor compartment and the other as an acceptor compartment for the quantification of molecular transport across the artificial cell membrane. However, synthetic phospholipids are overwhelmingly used to create DIBs instead of naturally derived phospholipids, even though the diverse distribution of phospholipids in the latter is more biomimetic. We present the first systematic study of the role of temperature in DIB formation, which shows that the temperature at which DIBs are formed is a key parameter for the formation of DIBs using naturally derived phospholipids in a microfluidic platform. The phospholipids that are most abundant in mammalian cell membranes (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI)) only form DIBs when the temperature is above the phase transition temperature (Tm). Similarly, DIB formation usually only occurs above the highest Tm of a single phospholipid in a bespoke formulation. In addition, we show a new phenomenon wherein the DIB "melts" without disintegrating for bilayers formed predominantly of phospholipids that occupy cylindrical spaces. We also demonstrate differences in DIB formation rates as well as permeability of these biomimetic membranes. Given the difficulties associated with making DIBs using naturally derived phospholipids, we anticipate this work will illuminate the role of phospholipid phase transition in mono- and bilayer formation and lay the foundation for DIBs to be used as human-mimetic artificial cell membranes.


Asunto(s)
Células Artificiales , Membrana Dobles de Lípidos , Biomimética , Membrana Celular , Humanos , Membranas Artificiales , Temperatura
3.
Langmuir ; 37(31): 9597-9604, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34328000

RESUMEN

Resistance to algae contamination is an important characteristic of insulators used in overhead power distribution in coastal environments. It is therefore important to understand the parameters governing algae adhesion onto polymer insulator materials such as silicone. Flow cell-based shear experiments were conducted in order to characterize the adhesion strength of algae onto polydimethylsiloxane surfaces, comparing fresh polymer substrates with those that have been soaked in water and saline solutions for 1 month. Both freshwater algae and seawater species could withstand considerably less drag force and were therefore more easily removed when the polymer was soaked in salt water. The polymer surface was found to be unaltered in terms of its roughness, contact angle, and lack of water uptake; no macroscopic surface characterization was therefore able to account for the differences in cell adhesion strength resulting from the soaking treatment. Surface-specific nonlinear vibrational spectroscopy, however, revealed subtle differences in the orientation of surface methyl groups that resulted from the water and saline exposure.


Asunto(s)
Polímeros , Siliconas , Adhesión Celular , Análisis Espectral , Propiedades de Superficie
4.
Lab Chip ; 20(17): 3279, 2020 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-32749429

RESUMEN

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.

5.
Lab Chip ; 20(11): 1898-1906, 2020 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-32322848

RESUMEN

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.


Asunto(s)
Células Artificiales , Preparaciones Farmacéuticas , Membrana Celular , Humanos , Membranas Artificiales , Microfluídica , Permeabilidad
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