Effect of Serotonin on Membranes Properties Studied by Molecular Dynamics Simulations

Extending the life of transfused red blood cells (RBC) has major implications in the treatment of several diseases (anemia, sickle cell disease) that require repeated transfusions. Recently, it has been demonstrated that serotonin (5-hydroxytryptamine), a monoamine neurotransmitter implicated in the central nervous system, has a protective role on red blood cells and is crucial to ensure normal erythropoiesis and red blood cells survival in mice. Without serotonin, the half-life of RBC is reduced both in vivo and in vitro. Among the mechanisms responsible for this effect, oxidation cascade plays a significant role. Serotonin could act as an antioxidant agent to prevent destabilization of the membrane and lipid peroxidation. Different hypotheses are advanced to investigate its protecting effect: How does serotonin prevent destabilization of membranes? What are the mechanisms in which serotonin interplays with lipid peroxidation?We present results related to the first question, i.e. how does serotonin interact with membranes. We performed molecular dynamics simulations with a protonated serotonin molecule initially placed in the solvent compartment of a fully hydrated bilayer of POPC. We observed that serotonin rapidly locates at the membrane interface. The key interaction is a salt bridge between the amine group of serotonin and the phosphate group of lipids with the aromatic group of serotonin pointing inward the bilayer. Simulations with several serotonins show no aggregation of the latter at the interface. Examination of different membrane properties shows a slight increase of the order parameter for the unsaturated chain. Analogs of serotonin molecules, which have increased or decreased protective effects compared to serotonin, are currently underway in similar conditions.