Interactions between model cell membranes and the neuroactive drug propofol

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:526

Article

Niga, Petru¹  Hansson-Mille, Petra M.¹  Swerin, Agne^1,2  Claesson, Per M.^1,2  Schoelkopf, Joachim³  Gane, Patrick A. C.^3,4  Bergendal, Erik²  Tummino, Andrea^5,6  Campbell, Richard A.⁵  Johnson, C. Magnus² 

[1] RISE Res Inst Sweden, Biosci & Mat Surface Proc & Formulat, Box 5607, SE-11428 Stockholm, Sweden

[2] KTH Royal Inst Technol, Dept Chem, Div Surface & Corros Sci, SE-10044 Stockholm, Sweden

[3] Omya Int AG, Baslerstr 42, CH-4665 Oftringen, Switzerland

[4] Aalto Univ, Sch Chem Engn, Dept Bioprod & Biosyst, POB 76300, FI-00076 Helsinki, Finland

[5] Inst Laue Langevin, 71 Ave Martyrs, F-38042 Grenoble, France

[6] Eotvos Lorand Univ, Budapest 112,POB 32, H-1518 Budapest, Hungary

关键词: Propofol;    Vibrational sum frequency spectroscopy;    Neutron reflectometry;    Small amphiphilic drug;    Model membrane;    Phospholipid monolayers;   

DOI  :  10.1016/j.jcis.2018.03.052

来源: Elsevier

【 摘 要 】

Vibrational sum frequency spectroscopy (VSFS) complemented by surface pressure isotherm and neutron reflectometry (NR) experiments were employed to investigate the interactions between propofol, a small amphiphilic molecule that currently is the most common general anaesthetic drug, and phospholipid monolayers. A series of biologically relevant saturated phospholipids of varying chain length from C-18 to C(14 )were spread on either pure water or propofol (2,6-bis(1-methylethyl)phenol) solution in a Langmuir trough, and the change in the molecular structure of the film, induced by the interaction with propofol, was studied with respect to the surface pressure. The results from the surface pressure isotherm experiments revealed that propofol, as long as it remains at the interface, enhances the fluidity of the phospholipid monolayer. The VSF spectra demonstrate that for each phospholipid the amount of propofol in the monolayer region decreases with increasing surface pressure. Such squeeze out is in contrast to the enhanced interactions that can be exhibited by more complex amphiphilic molecules such as peptides. At surface pressures of 22-25 mN m(-1), which are relevant for biological cell membranes, most of the propofol has been expelled from the monolayer, especially in the case of the C-16 and C-18 phospholipids that adopt a liquid condensed phase packing of its alkyl tails. At lower surface pressures of 5 mN m(-1), the effect of propofol on the structure of the alkyl tails is enhanced when the phospholipids are present in a liquid expanded phase. Specifically, for the C-16 phospholipid, NR data reveal that propofol is located exclusively in the head group region, which is rationalized in the context of previous studies. The results imply a non-homogeneous distribution of propofol in the plane of real cell membranes, which is an inference that requires urgent testing and may help to explain why such low concentration of the drug are required to induce general anaesthesia. (C) 2018 Elsevier Inc. All rights reserved.

【 授权许可】

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