Cholesterol sequestration by xenon nano bubbles leads to lipid raft destabilization

• Published in: Soft matter 2020-11, Vol.16 (42), p.9655-9661
• Main Authors: Reyes-Figueroa, A. D, Karttunen, Mikko, Ruiz-Suárez, J. C
• Format: Article
• Language: English
• Subjects: Anesthesia; Bubbles; Cholesterol; Destabilization; Distribution functions; Entropy; Hydrophobicity; Lipid rafts; Lipids; Molecular dynamics; Nucleation; Phosphocholine; Radial distribution; Rafts; Virial coefficients; Xenon
• ISSN: 1744-683X; 1744-6848
• DOI: 10.1039/d0sm01256d

Combined coarse-grained (CG) and atomistic molecular dynamics (MD) simulations were performed to study the interactions of xenon with model lipid rafts consisting of 1,2-dipalmitoyl- sn-glycero -3-phosphocholine (DPPC), 1,2-dilauroyl- sn-glycero -3-phosphocholine (DLPC) and cholesterol (Chol). At a concentration of 2 Xe/lipid we observed an unexpected result: spontaneous nucleation of Xe nano bubbles which rapidly plunged into the bilayer. In this process Chol, essential for raft stabilization, was pulled out from the raft into the hydrophobic zone. When concentration was further increased (3 Xe/lipid), the bubbles increase in size and disrupted both the membrane and raft. We computed the radial distribution functions, pair-wise potentials, second virial coefficients and Schlitter entropy to scrutinize the nature of the interactions. Our findings, concurring with a recent report on the origin of general anaesthesia (M. A. Pavel, E. N. Petersen, H. Wang, R. A. Lerner and S. B. Hansen, Proc. Natl. Acad. Sci. U. S. A. , 2020, 117 (24), 13757-13766), suggest that the well-known anaesthetic effect of Xe could be mediated by sequestration of Chol, which, in turn, compromises the stability of rafts where specialized proteins needed to produce the nervous signal are anchored. Combined coarse-grained (CG) and atomistic molecular dynamics (MD) simulations were performed to study the interactions of xenon with model lipid rafts consisting of DPPC, DLPC and Chol.