European Biophysics Journal

, 38:537

On the relationship between drug’s size, cell membrane mechanical properties and high levels of multi drug resistance: a comparison to published data

Biophysics Letter

DOI: 10.1007/s00249-008-0385-x

Cite this article as:
Rauch, C. Eur Biophys J (2009) 38: 537. doi:10.1007/s00249-008-0385-x


Multi drug resistance (MDR) or cross resistance to drugs was initially explained on the basis that MDR cells express drug transporters that expel membrane-embedded drugs. However, it is now clear that transporters are a single piece from a complex puzzle. An issue that has been solved recently is, given that these transporters have to handle drugs, why should a membrane-embedded drug and a transporter meet? To solve this problem, a theory has been suggested considering the interaction between the cell membrane mechanical properties and the size of drugs. In simple terms, this theory proposes that an excess in the packing of lipid in the inner leaflet of the membrane of MDR cells is responsible for blocking drugs mechanically as a function of their sizes at the membrane level, thus impairing their flux into the cytosol. In turn it is expected that this would allow any membrane embedded drug to diffuse toward transporters. The study concluded that the size of drugs is necessarily important regarding the mechanical interaction between the drug and the membrane, and likely to be central to MDR. Remarkably, an experimental study based on MDR and published years ago concluded that the molecular weight (MW) of drugs was central to MDR (Biedler and Riehm in Cancer Res 30:1174–1184, 1970). Given that size and MW are linked together, I have compared the former theory to the latter experimental data and demonstrate that, indeed, basic membrane mechanics is involved in high levels of cross resistance to drugs in Pgp expressing cells.


Endocytosis Phospholipid translocase Drug pumping and transporters Multi drug resistance Lipid packing Pgp 

Copyright information

© European Biophysical Societies' Association 2008

Authors and Affiliations

  1. 1.School of Veterinary Medicine and Science, Sutton Bonington CampusUniversity of NottinghamSutton BoningtonUK