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Mathematical modelling of lipid transbilayer movement in the human erythrocyte plasma membrane

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Abstract

A model is presented to simulate transverse lipid movement in the human erythrocyte membrane. The model is based on a system of differential equations describing the time-dependence of phospholipid redistribution and the steady state distribution between the inner and outer membrane monolayer. It takes into account several mechanisms of translocation: (i) ATP-dependent transport via the aminophospholipid translocase; (ii) protein-mediated facilitated and (iii) carrier independent transbilayer diffusion. A reasonable modelling of the known lipid asymmetry could only be achieved by introducing mechanism (iii). We have called this pathway the compensatory flux, which is proportional to the gradient of phospholipids between both membrane leaflets. Using realistic model parameters, the model allows the calculation of the transbilayer motion and distribution of endogenous phospholipids of the human erythrocyte membrane for several biologically relevant conditions. Moreover, the model can also be applied to experiments usually performed to assess phospholipid redistribution in biological membranes. Thus, it is possible to simulate transbilayer motion of exogenously added phospholipid analogues in erythrocyte membranes. Those experiments have been carried out here in parallel using spin labeled lipid analogues. The general application of this model to other membrane systems is outlined.

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Abbreviations

PBS:

phosphate buffered saline

DFP:

diisopropyl fluorophosphate

ESR:

electron spin resonance

RBC:

red blood cells

PC:

phosphatidylcholine

PE:

phosphatidylethanolamine

PS:

phosphatidylserine

SM:

sphingomyelin

(0,2)PC:

1-palmitoyl-2(4doxylpentanoyl)-PC

(0,2)PE:

1-palmitoyl-2(4-doxylpentanoyl)-PE

(0,2) PS:

1-palmitoyl-2(4-doxylpentanoyl)-PS

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Authors and Affiliations

  1. Humboldt University of Berlin, Department of Biology, Institute of Biophysics, Invalidenstrasse 42, O-1040, Berlin, Germany

    Reinhart Heinrich, Andreas Herrmann & Peter Müller

  2. University of Maribor, Ljubljana and Faculty of Education, “J. Stefan” Institute, Maribor, Slovenia

    Milan Brumen

Authors
  1. Milan Brumen
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  2. Reinhart Heinrich
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  3. Andreas Herrmann
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  4. Peter Müller
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Brumen, M., Heinrich, R., Herrmann, A. et al. Mathematical modelling of lipid transbilayer movement in the human erythrocyte plasma membrane. Eur Biophys J 22, 213–223 (1993). https://doi.org/10.1007/BF00185783

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  • DOI: https://doi.org/10.1007/BF00185783

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