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

机译:流变液滴界面双层膜(rheo-DIBs):通过旋转盘诱导的剪切应力探测未搅拌水层对膜渗透性的影响

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摘要

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.
机译:提出了一种新的流变液滴界面双层(rheo-DIB)设备,作为在生物脂质膜上施加剪切应力的工具。尽管它们具有影响高通量膜易位研究的令人兴奋的潜力,但使用DIB进行的通透性分析却忽略了未搅拌水层(UWL)的影响。但是,如本研究所示,忽略此现象可能会大大降低膜通透性测量值,从而反过来限制了它们预测关键过程(如跨脂质膜的药物转运速率)的能力。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的双层渗透性,从而诱导平行于DIB膜的流动。通过分析有效膜渗透率与施加应力之间的关系,可以使用这种模型膜方法首次确定固有膜渗透率和UWL厚度,从而释放DIB进行扩散分析的潜力。数值模拟也验证了结果。

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