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Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide

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Modulating the structure and properties of cell membranes : the molecular mechanism of action of dimethyl sulfoxide. / Gurtovenko, Andrey A.; Anwar, Jamshed.

In: Journal of Physical Chemistry B, Vol. 111, No. 35, 06.09.2007, p. 10453-10460.

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Gurtovenko, Andrey A. ; Anwar, Jamshed. / Modulating the structure and properties of cell membranes : the molecular mechanism of action of dimethyl sulfoxide. In: Journal of Physical Chemistry B. 2007 ; Vol. 111, No. 35. pp. 10453-10460.

Bibtex

@article{7198515cb3c5444f8a31ee17d458070f,
title = "Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide",
abstract = "Dimethyl sulfoxide (DMSO) is a small amphiphilic molecule which is widely employed in cell biology as an effective penetration enhancer, cell fusogen, and cryoprotectant. Despite the vast number of experimental studies, the molecular basis of its action on lipid membranes is still obscure. A recent simulation study employing coarse-grained models has suggested that DMSO induces pores in the membrane (Notman, R.; Noro, M.; O'Malley, B.; Anwar, J. J. Am. Chem. Soc. 2006,128,13982-13983). We report here the molecular mechanism for DMSO's interaction with phospholipid membranes ascertained from atomic-scale molecular dynamics simulations. DMSO is observed to exhibit three distinct modes of action, each over a different concentration range. At low concentrations, DMSO induces membrane thinning and increases fluidity of the membrane's hydrophobic core. At higher concentrations, DMSO induces transient water pores into the membrane. At still higher concentrations, individual lipid molecules are desorbed from the membrane followed by disintegration of the bilayer structure. The study provides further evidence that a key aspect of DMSO's mechanism of action is pore formation, which explains the significant enhancement in permeability of membranes to hydrophilic molecules by DMSO as well as DMSO's cryoprotectant activity. The reduction in the rigidity and the general disruption of the membrane induced by DMSO are considered to be prerequisites for membrane fusion processes. The findings also indicate that the choice of DMSO concentration for a given application is critical, as the concentration defines the specific mode of the solvent's action. Knowledge of the distinct modes of action of DMSO and associated concentration dependency should enable optimization of Current application protocols on a rational basis and also promote new applications for DMSO.",
keywords = "PHOSPHOLIPID-BILAYERS, PARTICLE MESH EWALD, DMSO, FUSION, SPECTROSCOPY, DYNAMICS SIMULATIONS, PORE FORMATION, LIPID-BILAYERS, DIMETHYLSULFOXIDE, TEMPERATURE",
author = "Gurtovenko, {Andrey A.} and Jamshed Anwar",
year = "2007",
month = "9",
day = "6",
doi = "10.1021/jp073113e",
language = "English",
volume = "111",
pages = "10453--10460",
journal = "Journal of Physical Chemistry B",
issn = "1520-6106",
publisher = "AMER CHEMICAL SOC",
number = "35",

}

RIS

TY - JOUR

T1 - Modulating the structure and properties of cell membranes

T2 - the molecular mechanism of action of dimethyl sulfoxide

AU - Gurtovenko, Andrey A.

AU - Anwar, Jamshed

PY - 2007/9/6

Y1 - 2007/9/6

N2 - Dimethyl sulfoxide (DMSO) is a small amphiphilic molecule which is widely employed in cell biology as an effective penetration enhancer, cell fusogen, and cryoprotectant. Despite the vast number of experimental studies, the molecular basis of its action on lipid membranes is still obscure. A recent simulation study employing coarse-grained models has suggested that DMSO induces pores in the membrane (Notman, R.; Noro, M.; O'Malley, B.; Anwar, J. J. Am. Chem. Soc. 2006,128,13982-13983). We report here the molecular mechanism for DMSO's interaction with phospholipid membranes ascertained from atomic-scale molecular dynamics simulations. DMSO is observed to exhibit three distinct modes of action, each over a different concentration range. At low concentrations, DMSO induces membrane thinning and increases fluidity of the membrane's hydrophobic core. At higher concentrations, DMSO induces transient water pores into the membrane. At still higher concentrations, individual lipid molecules are desorbed from the membrane followed by disintegration of the bilayer structure. The study provides further evidence that a key aspect of DMSO's mechanism of action is pore formation, which explains the significant enhancement in permeability of membranes to hydrophilic molecules by DMSO as well as DMSO's cryoprotectant activity. The reduction in the rigidity and the general disruption of the membrane induced by DMSO are considered to be prerequisites for membrane fusion processes. The findings also indicate that the choice of DMSO concentration for a given application is critical, as the concentration defines the specific mode of the solvent's action. Knowledge of the distinct modes of action of DMSO and associated concentration dependency should enable optimization of Current application protocols on a rational basis and also promote new applications for DMSO.

AB - Dimethyl sulfoxide (DMSO) is a small amphiphilic molecule which is widely employed in cell biology as an effective penetration enhancer, cell fusogen, and cryoprotectant. Despite the vast number of experimental studies, the molecular basis of its action on lipid membranes is still obscure. A recent simulation study employing coarse-grained models has suggested that DMSO induces pores in the membrane (Notman, R.; Noro, M.; O'Malley, B.; Anwar, J. J. Am. Chem. Soc. 2006,128,13982-13983). We report here the molecular mechanism for DMSO's interaction with phospholipid membranes ascertained from atomic-scale molecular dynamics simulations. DMSO is observed to exhibit three distinct modes of action, each over a different concentration range. At low concentrations, DMSO induces membrane thinning and increases fluidity of the membrane's hydrophobic core. At higher concentrations, DMSO induces transient water pores into the membrane. At still higher concentrations, individual lipid molecules are desorbed from the membrane followed by disintegration of the bilayer structure. The study provides further evidence that a key aspect of DMSO's mechanism of action is pore formation, which explains the significant enhancement in permeability of membranes to hydrophilic molecules by DMSO as well as DMSO's cryoprotectant activity. The reduction in the rigidity and the general disruption of the membrane induced by DMSO are considered to be prerequisites for membrane fusion processes. The findings also indicate that the choice of DMSO concentration for a given application is critical, as the concentration defines the specific mode of the solvent's action. Knowledge of the distinct modes of action of DMSO and associated concentration dependency should enable optimization of Current application protocols on a rational basis and also promote new applications for DMSO.

KW - PHOSPHOLIPID-BILAYERS

KW - PARTICLE MESH EWALD

KW - DMSO

KW - FUSION

KW - SPECTROSCOPY

KW - DYNAMICS SIMULATIONS

KW - PORE FORMATION

KW - LIPID-BILAYERS

KW - DIMETHYLSULFOXIDE

KW - TEMPERATURE

U2 - 10.1021/jp073113e

DO - 10.1021/jp073113e

M3 - Journal article

VL - 111

SP - 10453

EP - 10460

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 35

ER -