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流变学液滴界面双层膜（rheo-DIBs）：通过旋转盘诱导剪切应力探究未搅拌水层对膜通透性的影响

Rheological Droplet Interface Bilayers (rheo-DIBs): Probing the Unstirred Water Layer Effect on Membrane Permeability via Spinning Disk Induced Shear Stress.

作者信息

Barlow Nathan E, Bolognesi Guido, Haylock Stuart, Flemming Anthony J, Brooks Nicholas J, Barter Laura M C, Ces Oscar

机构信息

Department of Chemistry, Imperial College London, Exhibition Road South Kensington, London, SW7 2AZ, UK.

Institute of Chemical Biology, Imperial College London, Exhibition Road South Kensington, London, SW7 2AZ, UK.

出版信息

Sci Rep. 2017 Dec 14;7(1):17551. doi: 10.1038/s41598-017-17883-0.

DOI:10.1038/s41598-017-17883-0
PMID:29242597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5730560/
Abstract

A new rheological droplet interface bilayer (rheo-DIB) device is presented as a tool to apply shear stress on biological lipid membranes. Despite their exciting potential for affecting high-throughput membrane translocation studies, permeability assays conducted using DIBs have neglected the effect of the unstirred water layer (UWL). However as demonstrated in this study, neglecting this phenomenon can cause significant underestimates in membrane permeability measurements which in turn limits their ability to predict key processes such as drug translocation rates across lipid membranes. With the use of the rheo-DIB chip, the effective bilayer permeability can be modulated by applying shear stress to the droplet interfaces, inducing flow parallel to the DIB membranes. By analysing the relation between the effective membrane permeability and the applied stress, both the intrinsic membrane permeability and UWL thickness can be determined for the first time using this model membrane approach, thereby unlocking the potential of DIBs for undertaking diffusion assays. The results are also validated with numerical simulations.

摘要

一种新型流变学液滴界面双层（rheo-DIB）装置被提出作为一种对生物脂质膜施加剪切应力的工具。尽管它们在影响高通量膜转运研究方面具有令人兴奋的潜力，但使用液滴界面双层进行的渗透性测定忽略了未搅拌水层（UWL）的影响。然而，正如本研究所表明的，忽略这一现象会导致膜渗透性测量结果严重低估，进而限制了它们预测关键过程（如药物跨脂质膜转运速率）的能力。通过使用rheo-DIB芯片，可以通过对液滴界面施加剪切应力来调节有效双层渗透性，从而诱导平行于DIB膜的流动。通过分析有效膜渗透性与所施加应力之间的关系，首次使用这种模型膜方法可以确定固有膜渗透性和UWL厚度，从而释放液滴界面双层进行扩散测定的潜力。结果也通过数值模拟得到了验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/d8e167652f72/41598_2017_17883_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/ec24a227e2fa/41598_2017_17883_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/0ecc8e4e8907/41598_2017_17883_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/9397de3c49c1/41598_2017_17883_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/cc7f0eb78bd0/41598_2017_17883_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/f42e99049913/41598_2017_17883_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/eb020c9e37c4/41598_2017_17883_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/d8e167652f72/41598_2017_17883_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/ec24a227e2fa/41598_2017_17883_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/0ecc8e4e8907/41598_2017_17883_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/9397de3c49c1/41598_2017_17883_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/cc7f0eb78bd0/41598_2017_17883_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/f42e99049913/41598_2017_17883_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/eb020c9e37c4/41598_2017_17883_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10be/5730560/d8e167652f72/41598_2017_17883_Fig7_HTML.jpg

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