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. 2019 Nov 20;9(1):17214.
doi: 10.1038/s41598-019-53952-2.

Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

Semen Yesylevskyy  1   2 , Timothée Rivel  3 , Christophe Ramseyer  3
Affiliations

Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine

Semen Yesylevskyy et al. Sci Rep. .

Abstract

In this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown for the first time that permeability of the highly curved membrane increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results suggest that the membrane curvature could be an important factor of drug translocation through the membrane.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Simulated systems with the curvatures 0.2 nm−1 (top panel), 0.0 nm−1 (middle panel) and −0.2 nm−1 (bottom panel). Outer membrane leaflet is on top. PC is red, PE is blue, PS is violet, SM is orange and cholesterol is green (see Methods for definitions of abbreviations). N and P atoms of the lipid head group and the hydroxyl oxygen of cholesterol are shown as spheres. Black spheres show dummy particles which maintain the membrane shape. Black lines show approximate axes where the ligands are restrained during umbrella sampling simulations. Water molecules and ions are not shown for clarity.
Figure 2
Figure 2
Potentials of mean force for studied ligands. The error bars are shown as semi-transparent bands.
Figure 3
Figure 3
Diffusion coefficients of the studied ligands. The error bars are shown as semi-transparent bands.
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