Serotonergic drugs modulate the phase behavior of complex lipid bilayers
Guzel Musabirova1, Oskar Engberg2, Ankur Gupta3
1Institute for Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16/18, D-04107, Leipzig, Germany; Institute of Physics, Kazan (Volga Region) Federal University, 18 Kremlevskaya St, 420008, Kazan Kazan, Russian Federation.
Biochimie
|April 21, 2022
Summary
Serotonin drugs alter lipid membrane behavior, similar to serotonin itself. These drugs change membrane phase behavior and domain sizes, potentially affecting protein function and causing side effects.
Area of Science:
- Biochemistry
- Biophysics
- Pharmacology
Background:
- Serotonin, a neurotransmitter, traditionally signals via G protein-coupled receptors (GPCRs).
- Serotonin also interacts with lipid membranes, modulating their phase behavior.
- This study explores if serotonergic drugs mimic serotonin's membrane interactions.
Purpose of the Study:
- To investigate the effect of specific serotonergic drugs on model lipid membranes.
- To determine if these drugs modulate membrane phase behavior similarly to serotonin.
- To understand potential mechanisms behind drug side effects related to membrane interactions.
Main Methods:
- Utilized deuterium (2H) Nuclear Magnetic Resonance (NMR) spectroscopy.
- Examined phase behavior in model membranes composed of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC)/N-palmitoyl-D-erythro-sphingomyelin (PSM)/cholesterol.
- Employed Atomic Force Microscopy (AFM) and Raman spectroscopy to assess membrane mechanics and order.
Main Results:
- All tested serotonergic drugs induced changes in 2H NMR spectra, indicating altered membrane phase behavior.
- Drugs increased hydrophobic mismatch between lipid phases, leading to larger domain sizes.
- AFM and Raman spectroscopy confirmed changes in membrane order and mechanical properties.
Conclusions:
- Serotonergic drugs, like serotonin, can modulate the phase behavior of lipid membranes.
- These drug-induced membrane alterations may influence the function of membrane proteins.
- Findings provide insights into potential mechanisms for observed drug side effects.
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