Effect of a Local Anesthetic Lidocaine Hydrochloride on the Bilayer Structure of Phospholipids

Takeda, Koichi; Sano, You; Ichikawa, Sosaku; Hirata, Yasushi; Matsuki, Hitoshi; Kaneshina, Shoji

doi:10.5650/jos.58.369

Cited by 16 publications

(15 citation statements)

References 37 publications

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“…However, both schemes reproduce experimentally determined location of neutral lidocaine. 90,91 Other experimental studies have shown that anesthetics have a preference for the lipid tails close to the interface between the hydrophobic core and the polar head groups, 92 which the three mentioned simulations all agree with.…”

Section: Membrane Partitioningsupporting

confidence: 67%

Implicit inclusion of atomic polarization in modeling of partitioning between water and lipid bilayers

Jämbeck

Lyubartsev

2013

Phys. Chem. Chem. Phys.

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We propose an effective and straightforward way of including atomic polarization in simulations of the partitioning of small molecules in inhomogenous media based on classical molecular dynamics with non-polarizable force fields. The approach presented here takes advantage of the relatively fast sampling of phase space obtained with additive force fields by adding the polarization effects afterwards. By using pre-polarized charges for the polar and non-polar phases together with a polarization correction term the effects of atomic polarization are effectively taken into account. The results show a clear improvement compared to using the more common setup with one set of charges obtained from gas phase ab initio calculations. It is shown that when proper measures are taken into account computer simulations with non-polarizable force fields are able to accurately determine water-membrane partitioning and preferential location of small molecules in the membrane interior. We believe that the approach presented here can be useful in rational drug design and in investigations of molecular mechanisms of anesthetic or toxic action.

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Section: Membrane Partitioningsupporting

confidence: 67%

Implicit inclusion of atomic polarization in modeling of partitioning between water and lipid bilayers

Jämbeck

Lyubartsev

2013

Phys. Chem. Chem. Phys.

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“…For achieving this purpose, liposomes composed of egg L-α-phosphatidylcholine (EPC), cholesterol (CHOL), and sphingomyelin (SM) were used ( Figure 1). EPC is an egg yolk mixture of phosphatidylcholines which are the most abundant lipids in cell membranes [21][22][23]. Cholesterol and sphingomyelin are essential components of the human cell membranes [24,25], which undergo tight packing with phosphatidylcholines [26,27], forming the so called lipid rafts [28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol induces ordered domains formation in biomembranes: Implication for its pleiotropic action

Neves

Nunes

Reis

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Resveratrol is a polyphenol compound with great value in cancer therapy, cardiovascular protection, and neurodegenerative disorders. The mechanism by which resveratrol exerts such pleiotropic effects is not yet clear and there is a huge need to understand the influence of this compound on the regulation of lipid domains formation on membrane structure. The aim of the present study was to reveal potential molecular interactions between resveratrol and lipid rafts found in cell membranes by means of Förster resonance energy transfer, DPH fluorescence quenching, and triton X-100 detergent resistance assay. Liposomes composed of egg phosphatidylcholine, cholesterol, and sphingomyelin were used as model membranes. The results revealed that resveratrol induces phase separation and formation of liquid-ordered domains in bilayer structures. The formation of such tightly packed lipid rafts is important for different signal transduction pathways, through the regulation of membrane-associating proteins, that can justify several pharmacological activities of this compound.

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“…As such, the effect of anaesthetic molecules on cell membranes containing ion channels has been extensively studied. [13][14][15][16][17] Furthermore, it is still unknown how local anaethestics affect lipid raft domains. [1][2][3][4][5] Recently, local anaethestics have attracted significant attention.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9][10][11][12] In addition, interactions between anaethestics and the lipid bilayer, which surrounds the ion channels, have also been studied as it has been suggested that the perturbation of the lipids due to invasion of anaethestics disturbs the ion channel function. [13][14][15][16][17] Furthermore, it is still unknown how local anaethestics affect lipid raft domains. Lipid raft domains are mainly composed of saturated lipids, cholesterol and membrane proteins, such as ion channels, and are dispersed in cell membranes, which are thought to occur via phase separation.…”

Section: Introductionmentioning

confidence: 99%

Effect of dibucaine hydrochloride on raft-like lipid domains in model membrane systems

2015

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To clarify the biophysical and/or physicochemical mechanism of anaesthesia, we investigated the influence of dibucaine hydrochloride (DC·HCl), a local anaesthetic, on raft-like domains in ternary liposomes composed of dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol). The large DOPC/DPPC/Chol liposome is directly observable by optical microscopy and is known to be laterally separated into a liquid-ordered (Lo) phase (raft-like domain) and liquid-disordered (Ld) phase under certain conditions. Hence, it is useful for the study of lipid raft domains as a simple model system of cell membranes. We observed ternary liposomes with three concentrations (0, 0.05 and 0.2 mM) of DC·HCl at various temperatures and calculated the angle-averaged two-dimensional autocorrelation functions to confirm the change in miscibility transition temperature (T c ) of ternary liposomes. Furthermore, we calculated the circularity of the Lo domain to confirm the change in line tension of the Lo/Ld phase boundary. The results indicated that the insertion of DC molecules into lipid bilayers induces reduction in T c of the ternary liposome, accompanied by reduction in line tension of the phase boundary. This suggests that the DC·HCl molecules may disturb ion channel functions by affecting the lipid bilayers surrounding the ion channels. † Electronic supplementary information (ESI) available: Typical results of the 2D-AC analyses of liposomes with three types of phase patterns, a typical microscopic image of an ambiguous phase pattern, and result of Fourier analysis. See

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Effect of a Local Anesthetic Lidocaine Hydrochloride on the Bilayer Structure of Phospholipids

Cited by 16 publications

References 37 publications

Implicit inclusion of atomic polarization in modeling of partitioning between water and lipid bilayers

Implicit inclusion of atomic polarization in modeling of partitioning between water and lipid bilayers

Resveratrol induces ordered domains formation in biomembranes: Implication for its pleiotropic action

Effect of dibucaine hydrochloride on raft-like lipid domains in model membrane systems

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