Reinvestigation by Phosphorus NMR of Lipid Distribution in Bicelles

Mixtures of dimyristoyl-phosphatidylcholine (DMPC) and dihexanoyl-phosphatidylcholine (DHPC) in water form disks also called bicelles and different bilayer organizations when the mol ratio of the two lipids and the temperature are varied. The spontaneous alignment in a magnetic field of these bilayers above the transition temperature Tm of DMPC is an attractive property that was successfully used to investigate protein structure by NMR. In this article, we have attempted to give an overview of all structural transformations of DMPC/DHPC mixtures that can be inferred from broad band 31P-NMR spectroscopy between 5 and 60°C. We show that above a critical temperature, Tv, perforated vesicles progressively replace alignable structures. The holes in these vesicles disappear above a new temperature threshold, Th. The driving force for these temperature-dependent transformations that has been overlooked in previous studies is the increase of DHPC miscibility in the bilayer domain above Tm. Accordingly, we propose a new model (the “mixed bicelle” model) that emphasizes the consequence of the mixing. This investigation shows that the various structures of DMPC in the presence of increasing mol ratios of the short-chain DHPC is reminiscent of the observation put forward by several laboratories investigating solubilization and reconstitution of biological membranes.