Modulating the Structure and Properties of Cell Membranes: The Molecular Mechanism of Action of Dimethyl Sulfoxide

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• 作者：Andrey A. Gurtovenko ; Jamshed Anwar
• 刊名：Journal of Physical Chemistry B
• 出版年：2007
• 出版时间：September 6, 2007
• 年：2007
• 卷：111
• 期：35
• 页码：10453 - 10460
• 全文大小：1159K
• 年卷期：v.111,no.35(September 6, 2007)
• ISSN：1520-5207

文摘

Dimethyl sulfoxide (DMSO) is a small amphiphilic molecule which is widely employed in cell biology as aneffective penetration enhancer, cell fusogen, and cryoprotectant. Despite the vast number of experimentalstudies, the molecular basis of its action on lipid membranes is still obscure. A recent simulation studyemploying 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 molecularmechanism for DMSO's interaction with phospholipid membranes ascertained from atomic-scale moleculardynamics simulations. DMSO is observed to exhibit three distinct modes of action, each over a differentconcentration range. At low concentrations, DMSO induces membrane thinning and increases fluidity of themembrane's hydrophobic core. At higher concentrations, DMSO induces transient water pores into themembrane. At still higher concentrations, individual lipid molecules are desorbed from the membrane followedby disintegration of the bilayer structure. The study provides further evidence that a key aspect of DMSO'smechanism of action is pore formation, which explains the significant enhancement in permeability ofmembranes to hydrophilic molecules by DMSO as well as DMSO's cryoprotectant activity. The reduction inthe rigidity and the general disruption of the membrane induced by DMSO are considered to be prerequisitesfor membrane fusion processes. The findings also indicate that the choice of DMSO concentration for agiven application is critical, as the concentration defines the specific mode of the solvent's action. Knowledgeof the distinct modes of action of DMSO and associated concentration dependency should enable optimizationof current application protocols on a rational basis and also promote new applications for DMSO.