The aim of the project is to demonstrate experimentally the validity of this novel membrane architecture and explain the adaptation to hydrothermal stress in hyperthermophilic Archaea. To achieve this goal, we will compare the physico-chemical parameters of natural vs. reconstructed synthetic membranes, in presence or absence of apolar lipids, mimicking those of Archaea in order to identify the specific contribution of each lipid type, and each lipid moiety, on membrane stability. We will perform the total synthesis of di- and tetraether lipids. Working with synthetic lipids allows for the control of membrane composition and easier interpretation of molecular dynamics data, while working with natural lipids permits to test yet undetermined effects of polar headgroups/core lipids on membrane stability. Physical parameters will be determined from a combination of X-ray/neutron diffraction and diffusion, SAXS, Fourier-transform infrared (FTIR), fluorescence spectroscopies, liquid and solid state NMR and confocal fluorescence or electronic microscopies. The results will enable us to characterize the order parameters, size, shape and domain formation as well as permeability and viscosity of the lipid membranes. Due to the precise control of lipid compositions, variations in these parameter values can be readily attributed to specific lipid moieties. For the first time, it will allow the construction of a comprehensive model of the archaeal membrane and principles governing its stability, which will include a contribution for polar headgroups and apolar lipids.
The ArchaeoMembranes project addresses a fundamental question of general and philosophical interest concerning life under extreme environmental conditions, and in fine, about the origin of life on Earth. In this project, we propose the groundwork for a novel membrane architecture, which demonstration would constitute a major breakthrough in membrane science, and on how we understand the cellular membrane. Our preliminary results clearly show that such a membrane architecture can exist in vitro. Obtaining definitive proof that it leads to the expected physical and physiological behavior will have a major scientific echo in the community since it will shed a new light on membrane adaptation to extreme conditions. If this novel ultrastructure can be proven, it implies that lipid rafts, e.g. functionally distinct domains, may coexist in the membranes of Archaea, whose implications on cell physiology and functioning are numerous. Last, redefining the phase diagram of the membrane will also have concrete biotechnological applications.
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