Membrane biophysical properties and environmentally-sensitive probe

由脂质双分子层形成的细胞膜对生物学至关重要，但通常是从生物物理学的角度在物理或化学甚至材料科学系进行研究。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，人们对这些生物物理特性是如何调节的知之甚少。脂质双分子层可以存在于许多不同的阶段。有序和无序流体相的同时共存现在已经在模型双层中得到了很好的确立，并且在细胞膜中有大量证据，包括来自成像、生化和生物物理测量的数据。不同共存相的结构域涉及许多重要的生物和病理过程，包括免疫系统激活、病毒进入和退出以及细胞迁移。用于研究共存相的关键工具是荧光显微镜与荧光团耦合，荧光团根据其局部物理和化学环境改变其发射特性。这种染料已用于模型膜、固定细胞和活细胞以及整个生物体，以评估膜双层秩序。尽管如此，它从来没有证明探针本身如何影响所研究的膜的性质。也没有显示这些荧光团感知的环境特性（溶剂极性）如何与经常寻找的局部膜描述符相关：水合作用、顺序参数、分子迁移率和分配。本项目旨在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。一旦建立起来，研究人员将第一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.