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

膜脂不对称对于活细胞来说是至关重要的，以保持其生命功能。特定的膜蛋白，称为脂翻转酶，介导脂类跨细胞膜的运输，从而使膜脂对称性的产生和维持。目前的概念表明，脂质移位的动态过程也可能有助于控制膜域组织和驱动膜泡的形成。然而，这些概念缺乏直接的实验证据。需要开发适合于在明确定义的条件下研究这些膜转运体的复杂工具。在这个项目中，我们将建立一个基于巨大单层囊泡的重建系统。我们研究的中心目标是详细分析脂翻转酶的功能，以剖析它们在膜组织和形态调节中的作用。我们将探索在生理条件下，在功能脂翻转酶存在的情况下，细胞样脂类膜组合物的膜重组。我们将测量膜的物理性质，以响应这些膜转运蛋白的活性，并在大小长度尺度上分析膜介导的协同效应。我们期望仿生膜系统和成像方法的强大结合将为脂转肽酶转化为膜重塑过程提供重要的新见解。

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.