Hydrophobic Gating in Membrane Nanopores: Water at the Nanoscale

膜纳米孔中的疏水门控：纳米尺度的水

• 批准号: EP/R004722/1
• 负责人: Mark Sansom
• 金额: $ 48.38万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR004722%2F1
• 关键词: Hydrophobic; Gating; Membrane; Nanopores; Water

The properties of water play a key role in biology, underlying all aspects of cellular structure and function. All cells are surrounded by lipidic membranes, in which there exist pore-like proteins which allow communication and exchange between the inside and outside of cells. Such nanoscale pores ('nanopores') are of great importance both in cell biophysics and as potential components of novel biosensors. Nanopores are filled with water. However, water behaves differently on the nanoscale, inside pores whose diameter is 10 millionths of diameter that of a human hair. In particular, nanopores can undergo spontaneous de-wetting if their lining is sufficiently hydrophobic (i.e. 'oily'). This provides a possible way in which to control the activity of nanopores if we can control their wetting/de-wetting.We consequently need to understand and be able to model the physicochemical basis of wetting and de-wetting at a level of accuracy good enough for predictions to aid design of novel nanopores. This can be achieved by computer simulations - combining advanced algorithms and the power of modern supercomputers.In this way, we will determine the behaviour of water in nanopores, understanding how they can be functionally 'opened and closed' by wetting and de-wetting, and how the imposition of a voltage difference across a nanopore-containing membrane can cause the nanopores to electrowet, thereby switching them from an inactive (closed) to an active (open) state.This fundamental research will allow us to design controllable opening/closing of new nanopores for use in biosensors and other healthcare related applications.

水的性质在生物学中起着关键作用，是细胞结构和功能的各个方面的基础。所有的细胞都被脂膜包围，在脂膜中存在孔状蛋白质，允许细胞内外的沟通和交换。这种纳米尺度的孔在细胞生物物理学和新型生物传感器的潜在组成部分中都具有重要的意义。纳米孔中充满了水。然而，水在纳米尺度上的表现不同，在直径为人类头发直径的十万分之一的毛孔内。特别是，如果纳米孔的衬里具有足够的疏水性(即“油性”)，则纳米孔可以进行自发去湿。这提供了一种可能的方法来控制纳米孔的活动，如果我们能够控制它们的润湿/去湿。因此，我们需要理解和能够以足够准确的水平来模拟润湿和去湿的物理化学基础，以预测来辅助新型纳米孔的设计。这可以通过计算机模拟来实现--结合先进的算法和现代超级计算机的能力。通过这种方式，我们将确定纳米孔中水的行为，了解如何通过润湿和去湿来实现功能上的打开和关闭，以及在含有纳米孔的膜上施加电压差如何导致纳米孔电湿，从而将它们从非活动(关闭)状态切换到活动(打开)状态。这项基础研究将使我们能够设计可控的新纳米孔的打开/关闭，用于生物传感器和其他医疗保健相关应用。

项目成果

Cardiolipin, and not monolysocardiolipin, preferentially binds to the interface of complexes III and IV.

• DOI: 10.1039/d2sc04072g
• 发表时间: 2022-11-23
• 期刊: CHEMICAL SCIENCE
• 影响因子: 8.4
• 作者: Corey, Robin A. A.;Harrison, Noah;Stansfeld, Philllp J. J.;Sansom, Mark S. P.;Duncan, Anna L. L.
• 通讯作者: Duncan, Anna L. L.

Switching Cytolytic Nanopores into Antimicrobial Fractal Ruptures by a Single Side Chain Mutation.

通过单侧链突变将细胞溶解纳米孔切成抗菌分形破裂。

• DOI: 10.1021/acsnano.1c00218
• 发表时间: 2021-06-22
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Hammond K;Cipcigan F;Al Nahas K;Losasso V;Lewis H;Cama J;Martelli F;Simcock PW;Fletcher M;Ravi J;Stansfeld PJ;Pagliara S;Hoogenboom BW;Keyser UF;Sansom MSP;Crain J;Ryadnov MG
• 通讯作者: Ryadnov MG

Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix.

• DOI: 10.1021/acsnano.0c05960
• 发表时间: 2020-12-22
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Belessiotis-Richards A;Higgins SG;Sansom MSP;Alexander-Katz A;Stevens MM
• 通讯作者: Stevens MM

Effect of Water Models on Transmembrane Self-Assembled Cyclic Peptide Nanotubes.

• DOI: 10.1021/acsnano.1c00155
• 发表时间: 2021-04-27
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Calvelo M;Lynch CI;Granja JR;Sansom MSP;Garcia-Fandiño R
• 通讯作者: Garcia-Fandiño R

Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations.

• DOI: 10.1021/acs.jctc.1c00547
• 发表时间: 2021-10-12
• 期刊: Journal of chemical theory and computation
• 影响因子: 5.5
• 作者: Ansell TB;Curran L;Horrell MR;Pipatpolkai T;Letham SC;Song W;Siebold C;Stansfeld PJ;Sansom MSP;Corey RA
• 通讯作者: Corey RA