Biomembrane phase behavior and anhydrobiotic preservation in model membranes

Phase and mixing behavior of dilauroylphosphatidylcholine (DLPC)/distearoylphosphatidylcholine (DSPC) lipid bilayers have been studied at different length scales: by performing molecular dynamics simulations (MD) and fluorescence and surface probe microscopy in supported lipid bilayers (SLBs).;Local scale phase behavior (at the nanometer scale) was investigated using the Martini coarse grained molecular model. The mixing behavior of DLPC/DSPC reveals non linearity of the properties with respect to composition, with demixing in the fluid phase and in the gel phase. Variations in lipid structures were assessed through static and dynamic properties and allowed outlining for first time a molecular based phase diagram for DLPC/DSPC. Importantly, determination of the limiting values of the phase diagram depends on system size, simulation time and thermal history. Within the coexistence region we found dynamical heterogeneity indicating mesoscopic phase separation defined in contrast to macroscopic phase separations, where the lipid bilayers present domain sizes on the order of the matrix size. To obtain macroscopic phase separation, we created an alternative molecular model of a patterned bilayer. This allowed addressing dynamic variations of membrane lateral and transbilayer distribution in three gel phase domain patterns: symmetric domains, asymmetric domains and symmetric-asymmetric domains. Preferred bilayer configurations at the nano-scale are those that minimize the hydrophobic mismatch. By cluster analysis we observed that nano-scale patterns are dynamic structures, with mainly lateral and rotational diffusion affecting gel phase domain stability at the microsecond time scales.;For the same DLPC/DSPC system we also studied the impact of lipid symmetry on drying/rehydration reorganization in micrometer scale DSPC domains by characterizing lipid mobility and membrane microstructure. Experiments revealed phase behavior, drying rehydration transformations affecting bilayers and the avoidance of transformations by trehalose. SLBs with asymmetric domain configurations underwent major rearrangements during drying and rehydration, whereas the symmetric domain configuration mainly rearranged during rehydration. Taking all these studies together it clearly appears that a multiscale approach in lipid membrane model systems is valuable in understanding and interpreting the possible interactions of complex lipid mixtures in biological membranes.