Nanoclusters of Guest Molecules in Lipid Rafts of a Model Membrane Revealed by Pulsed Dipolar EPR Spectroscopy

• Published in: The journal of physical chemistry. B Vol. 129; no. 2; pp. 650 - 658
• Main Authors: Golysheva, Elena A., Kashnik, Anna S., Baranov, Denis S., Dzuba, Sergei A.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.01.2025
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - chemistry; adsorption; B: Biomaterials and Membranes; cholesterol; Cholesterol - chemistry; electron paramagnetic resonance spectroscopy; Electron Spin Resonance Spectroscopy; family; ibuprofen; Ibuprofen - chemistry; Lipid Bilayers - chemistry; lipid composition; liquids; Membrane Microdomains - chemistry; nanoparticles; Phosphatidylcholines - chemistry; phospholipids; Spin Labels
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/acs.jpcb.4c05217

Plasma membranes are known to segregate into liquid disordered and ordered nanoscale phases, the latter being called lipid rafts. The structure, lipid composition, and function of lipid rafts have been the subject of numerous studies using a variety of experimental and computational methods. Double electron–electron resonance (DEER, also known as PELDOR) is a member of the pulsed dipole EPR spectroscopy (PDS) family of techniques, allowing the study of nanoscale distances between spin-labeled molecules. To extend the possibilities of DEER in the study of molecule clusters, its joint application with the simple two-pulse electron spin echo (2p ESE) method is carried out here. We studied spin-labeled ibuprofen (ibuprofen-SL) diluted in bilayers composed of equimolar mixtures of dioleoyl-glycero-phosphocholine (DOPC) and dipalmitoyl-glycero-phosphocholine (DPPC) phospholipids, with added cholesterol, a system known as a raft-mimicking. The data obtained show that ibuprofen-SL molecules in this system form isolated clusters of about 4 nm in size, containing 6–8 molecules spaced at least 1.3 nm apart. These results indicate the interaction of ibuprofen-SL molecules with lipid rafts, for which the existence of nanoscale substructures at the boundaries of which adsorption of these molecules occurs is suggested.