User guide to the red blood cell model (RCM), a multiplatform JAVA-based model of human red blood cell homeostasis

Abstract

We introduce here a new multiplatform JAVA-based mathematical-computational model of RBC homeostasis for investigating the dynamics of changes in RBC homeostasis in health and disease. We provide a brief overview on the homeostasis of human RBCs and on the general biophysical principles guiding the modelling design. By way of a detailed tutorial we apply the model to investigate in depth the multiple effects associated with RBC dehydration induced by potassium permeabilization, a necessary preliminary for understanding the pathophysiology of a wide group of inherited haemolytic anaemias, a subject of intense current research and clinical interest. Using the red cell model (RCM), we design and run in silico representations of experimental protocols to study global RBC responses to calcium and potassium permeabilization covering a wide range of experimental, physiological and pathological conditions. Model outputs report the evolution in time of all the homeostatic variables in the system allowing, for the first time, a detailed and comprehensive account of the complex processes shaping global cell responses. Analysis of the results explains the mechanisms by which the entangled operation of all the RBC components link cell dehydration and protein crowding to cell acidification and to the generation of hypertonic, alkaline effluents. Open access to the RCM in a GitHub repository, together with the tutorial primed for a specific investigation pave the way for researchers and clinicians to apply the model on many different aspects of RBC physiology and pathology.