Membrane biophysical properties and environmentally-sensitive probe

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.