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On a biophysical and mathematical model of Pgp-mediated multidrug resistance: understanding the “space–time” dimension of MDR

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Abstract

Multidrug resistance (MDR) is explained by drug transporters with a drug-handling activity. Despite much work, MDR remains multifaceted, and several conditions are required to generate drug resistance. The drug pumping was conceptually described using a kinetic, i.e., temporal, approach. The re-emergence of physical biology has allowed us to take into account new parameters focusing on the notion of space. This, in turn, has given us important clues regarding the process whereby drug and transporter interact. We will demonstrate that the likelihood of drug-transporter meeting (i.e., the affinity) and thus interaction are also driven by the mechanical interaction between drug molecular weight (MW) and the membrane mechanical properties. This should allow us to mechanically control drug delivery.

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Notes

  1. Note that “spatial organization of a system” does refer also to dimensions that we will see are crucial to drug transporter meeting probability. Indeed, diffusion properties are different in 1, 2 or 3 dimensions.

  2. The efficiency defined at the molecular levels is referred as the number of products created per unit of time.

  3. Note that in the following text, surface pressure or tension will be used without conceptual difference. In both cases they refer to the mechanical packing of lipids in membrane leaflets.

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Acknowledgments

This work has been supported by the Medical Research Council (RA3805) and the University of Nottingham (NRF4305). Vasiliki Panagiotopoulou is supported by the Marie Curie early stage training network MMBNOTT. Finally we also thank Holly Broom (3rd Year veterinary student) for helping us re-read the paper and suggesting some modifications.

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Authors and Affiliations

  1. School of Mathematical Sciences, University of Nottingham, University Park, Nottingham, NG9 2RD, UK

    Vasiliki Panagiotopoulou & Oliver E. Jensen

  2. School of Mathematics, University of Southampton, University Road, Southampton, SO17 1BG, UK

    Giles Richardson

  3. School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, LE12 5RD, UK

    Cyril Rauch

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  1. Vasiliki Panagiotopoulou
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  2. Giles Richardson
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Correspondence to Cyril Rauch.

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Panagiotopoulou, V., Richardson, G., Jensen, O.E. et al. On a biophysical and mathematical model of Pgp-mediated multidrug resistance: understanding the “space–time” dimension of MDR. Eur Biophys J 39, 201–211 (2010). https://doi.org/10.1007/s00249-009-0555-5

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