Membrane biophysical properties and environmentally-sensitive probe

由脂质双层形成的细胞膜对生物学至关重要，但通常在物理或化学甚至材料科学部门内从生物物理学的角度进行研究。它们在细胞和环境之间形成选择性屏障，因此，它们的生物物理特性对其功能至关重要。尽管如此，很少有人知道这些生物物理特性是如何调节的。脂质双层可以存在于许多不同的相中。有序和无序的流体相的同时共存，现在已经很好地建立在模型双层，并有大量的证据，包括从成像，生物化学和生物物理测量的数据在细胞膜。不同共存阶段的结构域涉及许多重要的生物学和病理学过程，包括免疫系统激活、病毒进出和细胞迁移。用于研究共存相的一个关键工具是与荧光团结合的荧光显微镜，荧光团根据其局部物理和化学环境改变其发射特性。这种染料已被用于模型膜，固定和活细胞和整体，活生物体，以评估膜双层秩序。尽管如此，它从来没有被证明如何探针本身的影响所研究的膜的性质。它也没有被证明如何感测这些荧光团（溶剂极性）的环境属性涉及到当地的膜描述符经常寻求：水合作用，序参数，和分子的流动性和分区。该项目旨在通过结合先进的荧光显微镜和光谱测量以及分子动力学计算机模拟来建立这种关系。一旦建立，研究人员将首次能够以非侵入性的方式测量膜的特性，并对这些特性如何转化为生物学结果有一个清晰和定量的了解。

Cell membranes, formed from lipid bilayers are critically important to biology but are often studied from the perspective of biophysics within Departments of Physics or Chemistry or even Materials Science. They form the selective barriers between cells and their environments and as such, their biophysical properties are crucial to their function. Despite this, little is known about how these biophysical properties are regulated. Lipid bilayers can exist in a number of different phases. The simultaneous coexistence of ordered and disordered fluid phases is now well established in model bilayers and has substantial evidence in cell membranes including data from imaging, biochemical and biophysical measurements. Domains of different coexisting phases have been implicated in a number of important biological and pathological processes including immune system activation, virus entry and exit and cell migration. A key tool used to study coexisting phases is fluorescence microscopy coupled with fluorophores, which change their emission properties based on their local physical and chemical environments. Such dyes have been used in model membranes, fixed and live cells and whole, living organisms to assess membrane bilayer order. Despite this, it has never been demonstrated how the probes themselves influence the properties of the membrane under study. Nor has it been shown how the environmental property sensed by these fluorophores (solvent polarity) relates to the local membrane descriptors frequently sought: hydration, order parameter, and molecular mobility and partitioning. This project aims to establish this relationship using a combination of advanced fluorescence microscopy and spectroscopy measurements together with molecular dynamics computer simulations. Once established, researchers will, for the first time, be able to measure the properties of membranes in a non-invasive way and have a clear and quantitative understanding of how those properties translate into biological outcomes.