The asymmetry of plasma membranes and their cholesterol content influence the uptake of cisplatin

Sci Rep. 2019 Apr 4;9(1):5627. doi: 10.1038/s41598-019-41903-w.

Abstract

The composition of the plasma membrane of malignant cells is thought to influence the cellular uptake of cisplatin and to take part in developing resistance to this widespread anti-cancer drug. In this work we study the permeation of cisplatin through the model membranes of normal and cancer cells using molecular dynamics simulations. A special attention is paid to lipid asymmetry and cholesterol content of the membranes. The loss of lipid asymmetry, which is common for cancer cells, leads to a decrease in their permeability to cisplatin by one order of magnitude in comparison to the membranes of normal cells. The change in the cholesterol molar ratio from 0% to 33% also decreases the permeability of the membrane by approximately one order of magnitude. The permeability of pure DOPC membrane is 5-6 orders of magnitude higher than one of the membranes with realistic lipid composition, which makes it as an inadequate model for the studies of drug permeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biochemical Phenomena
  • Biological Transport
  • Cell Membrane / metabolism*
  • Cell Membrane / physiology
  • Cell Membrane Permeability
  • Cholesterol / metabolism*
  • Cisplatin / metabolism*
  • Cisplatin / pharmacology
  • Humans
  • Lipid Bilayers / metabolism
  • Models, Theoretical
  • Molecular Dynamics Simulation
  • Phospholipids / metabolism

Substances

  • Lipid Bilayers
  • Phospholipids
  • Cholesterol
  • Cisplatin