Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

10-POS Board 10 EFFECT OF SEROTONIN ON SPONTANEOUS MEMBRANE DOMAIN FORMATION Astrid F Brandner 1 ; Anna Bochicchio 1 ; Oskar Engberg 2 ; Daniel Huster 2 ; Rainer A Böckmann 1,3 ; 1 Friedrich-Alexander Universität Erlangen-Nürnberg, Computational Biology, Erlangen, Germany 2 University of Leipzig, Institute for Medical Physics and Biophysics, Leipzig, Germany 3 Erlangen National High Performance Computing Center, Erlangen, Germany Biomembranes exist in a variety of lipid and protein composition and have a dynamical behaviour to respond to different stimuli. The existence of defined regions or domains with specific structural and dynamical properties were shown to be associated with protein receptor localisation and signalling. Despite their importance e.g. in immune signalling, only little is known about the composition and dynamics of membrane domains. Their transient existence and nanometre scale make them methodologically challenging to identifying highly dynamic domains on the nanometer scale. In this work, by means of atomistic molecular dynamic simulations, we characterized the unbiased spontaneous formation of nanodomains in a plasma membrane model containing phosphatidylcholine, palmitoyl-sphingomyelin and cholesterol at different temperatures in presence or in absence of the neurotransmitter serotonin[1,2]. We show that serotonin binding to the membrane decreases the phase transition temperature. It affects domain composition and domain ordering as well as results in a decreased membrane elasticity. Our results suggest a novel mode of action of neurotransmitters in neuronal signal transmission. We followed the initial steps of nanodomains formation at the microsecond scale starting from a random mixture of lipids. Upon serotonin binding to the membrane, the domain order and composition was affected, resulting in a PC-enrichment of the disordered domains and a decreased membrane elasticity. Overall, we show that binding of serotonin to the membrane decreases the phase transition temperature as well as a modified lipid composition in the domains. Our simulations suggest a novel mode of action of neurotransmitters in neuronal signal transmission. [1] Engberg, O., Bochicchio, A., Brandner, A., Gupta, A., Dey, S., Böckmann, R. Huster, D. (2020). Serotonin Alters the Phase Equilibrium of a Ternary Mixture of Phospholipids and Cholesterol. Frontiers in Physiology, 11. [2] Bochicchio, A., Brandner, A., Engberg, O., Huster, D., & Böckmann, R. (2020). Spontaneous Membrane Nanodomain Formation in the Absence or Presence of the Neurotransmitter Serotonin. Frontiers in Cell and Developmental Biology, 8.

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