DOE OSTI · 3030428
Melatonin-Induced Modulation of Cholesterol-Enriched Model Neuronal Membranes
Abstract
Melatonin, a hormone primarily produced by the brain’s pineal gland, not only regulates circadian rhythms, but also influences the structural and biophysical properties of neuronal membranes. Its amphiphilic nature enables direct incorporation into lipid bilayers and preferential interactions with cholesterol-rich lipid rafts, critical hubs for cellular signaling and membrane organization. Despite increasing recognition of its membrane activity, the molecular basis of melatonin’s interactions with coexisting liquid-ordered (L o ) and liquid-disordered (L d ) phases remains unclear. Here, in this study, we combine small-angle neutron scattering (SANS) and all-atom molecular dynamics simulations to examine model neuronal membranes composed of DSPC, DOPC, POPC, and cholesterol. Our results show that melatonin preserves domain morphology while adopting distinct orientations within the bilayer and at the membrane interface, allowing both lateral and transmembrane bridging across lipid phases. These findings establish the molecular underpinnings of melatonin’s modulation of membrane heterogeneity and provide strong support for its receptor-independent actions.
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Bolmatov, Dima [Texas Tech University, Lubbock, TX (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)] (ORCID:0000000341798971), Reiter, Russel J. [Univ. of Texas at San Antonio, TX (United States)], Zav’yalov, Dmitry [Volgograd State Technical University (Russian Federation)], Do, Changwoo [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)] (ORCID:0000000183588417), Nagy, Gergely [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)] (ORCID:0000000327420198), Collier, Charles Patrick [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS)] (ORCID:000000028198793X), Katsaras, John [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)] (ORCID:0000000289374177), Lavrentovich, Maxim O. [Worcester State University, MA (United States); University of Tennessee, Knoxville, TN (United States)] (ORCID:0000000251257979). 2026-02-18. Melatonin-Induced Modulation of Cholesterol-Enriched Model Neuronal Membranes. https://doi.org/10.1021/acschemneuro.5c00682
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