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. 2011 Jul 6;101(1):110-7.
doi: 10.1016/j.bpj.2011.05.038.

Transfer of arginine into lipid bilayers is nonadditive

Justin L MacCallum  1 , W F Drew Bennett, D Peter Tieleman
Affiliations

Transfer of arginine into lipid bilayers is nonadditive

Justin L MacCallum et al. Biophys J. .

Abstract

Computer simulations suggest that the translocation of arginine through the hydrocarbon core of a lipid membrane proceeds by the formation of a water-filled defect that keeps the arginine molecule hydrated even at the center of the bilayer. We show here that adding additional arginine molecules into one of these water defects causes only a small change in free energy. The barrier for transferring multiple arginines through the membrane is approximately the same as for a single arginine and may even be lower depending on the exact geometry of the system. We discuss these results in the context of arginine-rich peptides such as antimicrobial and cell-penetrating peptides.

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Figures

Figure 1
Figure 1
Free energy to transfer an arginine from water into a DOPC lipid bilayer: (top) a single arginine; (middle) a second arginine with the first arginine fixed at the center of the bilayer; (bottom) a third arginine with the first arginine fixed at the center of the bilayer and the second arginine at 0.35 nm from the center. Shading indicates the standard error.
Figure 2
Figure 2
Number of oxygen atoms in the first hydration shell (out to 0.46 nm) of the first and second arginine molecules as a function of depth in the bilayer.
Figure 3
Figure 3
Number of hydrogen bonds to arginine as a function of depth in the bilayer. Shading indicates the standard error.
Figure 4
Figure 4
Free energy of transferring arginine from the interfacial minimum into cyclohexane (solid; red) or a DOPC bilayer (dashed; black). The cyclohexane-water system is described in the text. Both free energy profiles are aligned at the interfacial minimum. Shading indicates the standard error.
Figure 5
Figure 5
Free energy to transfer an arginine from water into cyclohexane. Shading indicates standard error.
Figure 6
Figure 6
Density of phosphorous (top) or water (bottom) depending on how many arginine molecules are located near the center of the bilayer.
Figure 7
Figure 7
Free energy to transfer a di-arginine from water into the center of a DOPC bilayer. The geometry of the di-arginine construct is described in the text.
See this image and copyright information in PMC

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