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ms_cisplatin_DOPC.pdf (1.2 MB)

The Permeation Mechanism of Cisplatin through a Dioleoylphosphocholine Bilayer

preprint
revised on 18.02.2021, 07:22 and posted on 19.02.2021, 04:59 by Lorena Ruano, Gustavo Cárdenas, Juan Jose Nogueira
The investigation of the intermolecular interactions between platinum-based anticancer drugs and lipid bilayers is of special relevance to unveil the mechanisms involved in different steps of the anticancer mode of action of these drugs. We have simulated the permeation of cisplatin through a model membrane composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids by means of umbrella sampling classical molecular dynamics simulations. The initial physisorption of cisplatin into the polar region of the lipid membrane is controlled, in a first moment, by long-range electrostatic interactions with the choline groups and, in a second step, by long-range electrostatic and hydrogen bond interactions with the phosphate groups. The second half of the permeation pathway, in which cisplatin diffuses through the nonpolar region of the bilayer, is characterized by the drop of the interactions with the polar heads and the rise of attractive interactions with the non-polar tails, which are dominated by van der Waals contributions.

Funding

Attraction of Talent Program 2018 of the Comunidad de Madrid, grant reference 2018-T1/BMD-10261

History

Email Address of Submitting Author

juan.nogueira@uam.es

Institution

Universidad Autonoma de Madrid

Country

Spain

ORCID For Submitting Author

0000-0001-7419-5670

Declaration of Conflict of Interest

No conflict of interest

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