Dielectric polarization properties of biological molecules on the nanoscale

这项研究将开发新的纳米尺度工具，用于在分子尺度上原位测量和成像生物分子的介电极化特性。这些性质是迄今尚不清楚的基本物理性质，因为。由于缺乏信息，在如此小的尺度上测量介电响应是非常困难的。标准工具仅限于微米量级，因此无法获取此类信息。在过去的几年里，这位主管开创了扫描介电显微镜(SDM)，这是一种能够测量小至几十纳米的纳米物体的介电性质的新技术--其分辨率在世界范围内是无与伦比的[1-3]。现在最大的挑战是进一步突破这项技术的界限，探索生物分子的极化率，特别是分子尺度上的生命分子(水、DNA、蛋白质)，这是本研究的目的。这些分子的介电性质是理解静电相互作用的迫切需要，静电相互作用是分子溶剂化、水化、结构和官能化等关键现象的基础。这项研究的目标将通过该主管以前的工作来实现，在该工作中，她首次测量了病毒内凝聚的DNA的介电常数[2]和限制在二维(2D)纳米通道内的水的介电常数[3]。具体地说，人们将寻求新的SDM装置来提高该技术的灵敏度，并探索单个生物分子的介电性质。学生将帮助开发所需的工具，并在导师的帮助下将其应用于研究大分子的介电性质。这项研究具有开创性，具有很强的交叉学科，将实验和理论物理、物理化学、分子生物学和两项纳米科学新技术结合在一起：导师首创的扫描介电显微镜，以及曼彻斯特大学凝聚物组和国家石墨烯研究所的2D材料技术。将产生的实验信息和工具将引起从事广泛学科工作的学术和工业用户的主要兴趣，特别是在英国和海外的生命科学(生物物理、分子生物学和生物医学)、表面科学和化学。特别是，这项研究将使与医疗保健相关的领域取得科学和技术进步。介电极化特性决定了生命分子的分子结构，如DNA和蛋白质构象，以及分子相互作用，如DNA与临床重要药物的相互作用。这项研究将使人们能够在分子水平上获得新的见解。这反过来应导致针对重要疾病的新药和新的分子传感技术的开发。这项研究还将使物理科学取得重要进展，提高我们对限制下分子溶剂化和输运的理解，这是现代物理和胶体化学以及纳米流体学等新兴领域的主要问题。参考文献[1]Fumagalli，L.，Esteban-Ferrer，D.，Cuervo，A.，Carrascosa，J.L.，Gomila，G.单个介电纳米粒子和具有超弱极化力的病毒的无标记识别。自然界的主宰。11,808-816(2012).[2]ACuervo，PD Dans，JL Carrascoa，M Orozco，G Gomila，L Fumagalli直接测量DNA proc的介电极化特性.娜塔莉。阿卡德。[3]Fumagalli，L.，Esfan diar，A.，Fabregas，R.，Hu，S.，Ares，P.，Janardanan，A.，Yang，Q.，Radha，B.，Taniguchi，T.，Watanabe，K.，Gomila，G.，Novoselov，K.S.，Geim，A.K.《科学》360,1339(2018)。

This research will develop new nanoscale tools for in situ measurement and imaging of the dielectric polarization properties of biomolecules on the molecular scale. These properties are fundamental physical properties remained unknown so far owing. The lack of information is for great difficulties in measuring a dielectric response on such a small scale. Standard tools are limited to the micrometer scale and, therefore, are unable to access such information. In the last years, the supervisor pioneered scanning dielectric microscopy (SDM), a novel technique able to measure the dielectric properties of nano-objects as small as few tens of nanometers - a resolution unparalleled world-wide [1-3]. The grand challenge is now to further push the boundaries of this technique and probe the polarizability of biomolecules, in particular the molecules of Life (water, DNA, proteins) on the molecular scale, which is the aim of this research. The dielectric properties of these molecules are urgently needed to understand electrostatic interactions which underpin crucial phenomena such as molecular solvation, hydration, structuring and functionalities. The objective of this research will be achieved by building on the previous work of the supervisor, in which she measured for the first time the dielectric constant of DNA condensed inside a virus [2] and of water confined inside two-dimensional (2D) nanochannels [3]. Specifically novel SDM setups will be pursued to increase the sensitivity of the technique and probe the dielectric properties of single biomolecules. The student will help developing the required tools and apply them to study of the dielectric properties of the macromolecules with the help of the supervisor.This research is groundbreaking and strongly interdisciplinary, bringing together experimental and theoretical physics, physical chemistry, molecular biology and two new technologies of nanoscience: scanning dielectric microscopy, which the supervisor pioneered, and the 2D-materials technology of the Condensed Matter Group and National Graphene Institute of the University of Manchester. The experimental information and tools that will be generated will be of major interest for academic and industrial users working in a wide range of disciplines, in particular Life sciences (biophysics, molecular biology and biomedicine), surface science and chemistry, both within the UK and overseas. In particular, the research will allow scientific and technological advances in areas related to health care. The dielectric polarization properties determine the molecular structure of the molecules of Life, such as DNA and protein conformations, and molecular interactions like those of DNA with clinically-important drugs. This research will allow gaining new insight on the molecular level. This in turn should lead to the development of new drugs against important diseases and of new molecular sensing technologies. This research will also allow important advances in physical sciences, improving our understanding of molecular solvation and transport under confinement, which are main issues of modern physical and colloid chemistry and of new emerging fields like nanofluidics. References [1] Fumagalli, L., Esteban-Ferrer, D., Cuervo, A., Carrascosa, J. L., Gomila, G. Label-free identification of single dielectric nanoparticles and viruses with ultraweak polarization forces. Nature Mater. 11, 808-816 (2012).[2] A Cuervo, PD Dans, JL Carrascosa, M Orozco, G Gomila, L Fumagalli Direct measurement of the dielectric polarization properties of DNA Proc. Natl. Acad. Sci 111, E3624-E3630 (2014).[3] Fumagalli, L., Esfandiar, A., Fabregas, R. , Hu, S., Ares, P., Janardanan, A., Yang, Q., Radha, B., Taniguchi, T., Watanabe, K., Gomila, G., Novoselov, K. S., Geim, A. K. Anomausly low dielectric constant of confined water. Science 360, 1339 (2018).