Biophysical Characterization Of Phosphatidyl Alcohols In Model Membranes-Effects Of Headgroup Size

The polymorphic phase behavior of different phospholipids depends strongly on fine details of their head group and backbone structures. Studies of phospholipid head group modification offers an attractive strategy in elucidating how structural elements of the head group effect membrane properties. We are investigating phosphatidyl alcohols with saturated fatty acyl chains and their interactions with phospholipids and sterols. Molecules of interest are dipalmitoyl glycerophospholipids with methanol, ethanol, propanol and butanol as different headgroups. These molecules can be formed from e.g., corresponding phosphatidylcholines due to the transphosphatidylation activity of phospholipase D. Phosphatidyl ethanol is of physiological relevance since it is increasingly formed in cells of chronic alcoholics. Thermodynamic properties such as phase transition temperatures, heat capacity of transitions and transition cooperativity have been studied with high sensitivity differential scanning calorimetry (DSC). The miscibility and effects of cholesterol on mixtures of these negatively charged phospholipids with high Tm and low Tm phospholipids have been determined using DSC, and with fluorescence spectroscopy using domain-selective lipid probes. The relative acyl-chain order in the bilayer membranes has been assessed using steady-state DPH anisotropy. We will report on the phase behavior of these molecules in simple and more complex bilayer systems. The formation, by the dipalmitoyl phosphatidyl alcohols, of sterol-enriched or ordered domains in fluid bilayer membranes will also be determined. Comparison of the properties of these phosphatidyl alcohols with molecules having closely related structures will help in understanding the relationships between the chemical structures, physical properties and functional properties of the phospholipid molecules in model as well as biological membranes.