The effects of melatonin, serotonin, tryptophan and NAS on the biophysical properties of DPPC monolayers.

Melatonin is a neurohormone that has been shown to be protective in Alzheimer's diseases against amyloid-β (Aβ) toxicity, which involves interaction of Aβ with neuronal membrane. Non-specific interactions of melatonin with cell membrane may play a physiological role in this process by preserving membrane fluidity. In the brain, melatonin is derived from the amino acid tryptophan through a pathway that includes serotonin and N-acetylserotonin (NAS). How these molecules affect the membrane properties is not understood. In this work, we studied interactions of melatonin and its metabolic precursors tryptophan, serotonin and NAS with dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface using Langmuir monolayer technique. Analysis of compression isotherms, phase transitions and compressibility moduli indicate that all four molecules alter the DPPC monolayer properties in a structure and concentration dependent manner. This effect was most pronounced for melatonin followed by NAS. Melatonin and NAS both decreased the compressibility modulus and shifted the LE/LC phase transition suggesting an increase in the membrane fluidity. Tryptophan and serotonin caused less pronounced effects on the DPPC isotherm. These differences suggest different interaction mechanisms and may be attributed to the interplay between electrostatic and hydrophobic interactions of these molecules with the zwitterionic DPPC headgroups which correlate with water solubility and oil partition coefficients (LogS and LogP) of each the four molecules. The results here demonstrate how the physiochemical properties of indoles can affect lipid membranes which may shed light on the functional significance of these important neurochemicals and the neuroprotective mechanisms of melatonin.