Crosstalk between membrane organization and multi-sphere morphologies of complex membranes

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Membrane lipid asymmetry is of paramount importance to the living cell in order to preserve its vital functions. Specific membrane proteins, termed lipid flippases, mediate the transport of lipids across cellular membranes and thereby enable the generation and maintenance of membrane lipid symmetry. Current concepts suggests that the dynamic process of lipid translocation may also help in controlling membrane domain organization and drive membrane vesicle formation. However, direct experimental evidence for these concepts is lacking. There is a need for the development of sophisticated tools that are suitable for studying these membrane transporters under well-defined conditions. In this project, we will establish a reconstitution system based on giant unilamellar vesicles. The central goal of our studies is a detailed functional analysis of lipid flippases in order to dissect their role in the regulation of membrane organization and morphology. We will explore membrane reorganization in the presence of functional lipid flippases under physiological conditions for cell-like lipid membrane compositions. We will measure the physical properties of membranes in response to the activity of these membrane transporters and analyze membrane-mediated cooperative effects at large and small length scales. We expect the powerful combination of biomimetic membrane systems and imaging methods to provide important new insights into the processes of into membrane reshaping processes by lipid flippases.