The Effect of Serotonin on the Lateral Segregation of a Raft Membrane Mixture

Abstract

Lipids may laterally segregate in membranes, especially in the presence of cholesterol. In cells, a vast diversity of molecules, such as proteins, neurotransmitters, and hormones could also affect the lateral segregation of the individual lipid molecules. Serotonin is an important neurotransmitter for physiological brain function. Serotonin has several physiological membrane receptors but has recently been shown to also bind to membranes with high affinity. Consequently, serotonin could also affect the membranes through indirect interactions among lipids or by changing lipid-lipid interactions. In this study, we have used 2H NMR to characterise, the effect of serotonin on the lateral segregation in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)/Palmitoyl-sphingomyelin/cholesterol bilayers by deuterating the individual lipids species. In addition, we have studied the membrane distribution of serotonin in POPC bilayers using 1H NOESY NMR under magic-angle spinning conditions to understand the molecular details of serotonin-lipid interaction. We observed a clear effect of serotonin on phase separation as observed in the 2H NMR spectra of the the samples studied. In conclusion, serotonin influences lateral segregation that could be relevant for its physiological function. We will discuss the effect of serotonin on the individual lipid species studied.