Theoretical model of reticulocyte to erythrocyte shape transformation

A theoretical model describing the kinetics of reticulocyte shape transformation was developed. The model considers the evolution of a simple cellular shape under transmembrane pressure difference, and proposes a four-parameter axisymmetric approximation of the cell surface. The mathematical analysis considers plasma membrane tension in the plane of bilayer leaflets, membrane spontaneous curvature and transmembrane transport of water. Cytoskeleton dilatational and shear rigidity, and the energetic barrier preventing the decrease of cell volume below a certain minimum are also incorporated. The set of adequate physical assumptions allowed for formulation of the equation for free energy of the investigated system. Computer simulations of cell shape changes, down to the state of free energy minimum, together with estimation of the time needed for the resulting transport of water, revealed a complex, three-phase picture of temporal alterations in cellular geometry with a wide spectrum of final results, and led to propose a standard model of reticulocyte–erythrocyte transformation. According to the model, both cell volume and surface undergo changes, and the work of the pressure, initially accumulated in the cytoskeleton, is consumed for local bending of the cell membrane. Further simulations with modified initial shape or parameters of the standard model show the trajectories of system evolution and help in better understanding the conditions for the erythro-, sphero-, ovalo-, stomato-, and leptoidal metamorphosis of maturing red blood cells. The stability of the final biconcave shape was also verified. Spherogenic modifications were discussed in the context of spherocytosis. Future development of the model was proposed.