The Study of Nanoscopic Phase Separation in Lipid Mixtures using Small Angle Neutron Scattering

In biological membranes the lipid composition is extraordinarily complex, which provides proteins with the optimal lipid micro environment for physiological activity. The complexity of lipid composition and the consequences for biological systems has attracted significant interest in the past four decades, particularly in the realm of nanoscopic phase coexistence. Nanoscale phase separated domains in the plasma membrane are significant due to their critical roles in cell trafficking and signaling functionality. In this thesis, we chose to revisit a simple binary mixture of lipids (DPPC and DLPC), whose relevance persists since some biological systems can be relatively simple, composed of only a few different lipid species. Moreover, this system exhibits patterned phase separation at a macroscale similar to that of more complex lipid mixtures. Using calorimetry, densitometry and small angle neutron scattering (SANS) we were able to revisit the phase diagram for this system. The nanoscale domain structures on the vesicles captured by SANS were characterized using an ab-initio fitting program (MONSA). The analysis revealed that the molecular volumes of the lipids are not simply additive relative to their behavior in single lipid systems but depend on molecule-to-molecule packing interactions in the different domain regions that coexist in the membrane.