MODELING OF PHOSPHOLIPID TRANSLOCATION IN THE ERYTHROCYTE-MEMBRANE - A COMBINED KINETIC AND THERMODYNAMIC APPROACH

A mathematical model for the dynamics of transbilayer movements of lip ids in the erythrocyte plasma membrane is presented. It takes into acc ount an active carrier which mediates the ATP-dependent translocation of phosphatidylserine and phosphatidylethanolamine from the outer to t he cytoplasmic leaflet of the membrane and passive fluxes of these lip ids as well as of phosphatidylcholine, sphingomyelin and cholesterol b etween both layers. It is assumed that the passive fluxes are driven b y concentration gradients of the lipids and by mechanical forces which result from area limitation for lipid occupation in both leaflets. Co mpared with a previous mathematical treatment of lipid translocation p rocesses in the erythrocyte membrane the present model is much closer to realistic conditions, e.g. concerning the number of lipid species i nvolved. Furthermore, the use of linear flux-force relationships as kn own from irreversible thermodynamics allows a simpler treatment of the passive fluxes than before and provides a relevant framework: to stud y the coupling between the various processes. The model allows to simu late the time dependent changes of lipid concentrations which take pla ce after activation or inhibition of ATP-dependent translocation. Usin g realistic parameter values it explains in quantitative terms the sta tionary asymmetric distribution of lipids under in vivo conditions. Us ing principles of metabolic control analysis we are able to quantify t he role of the various active and passive processes in determining the asymmetric distribution for each lipid species. (C) 1997 Academic Pre ss Limited.