Mathematical modeling of intracellular membrane transport: Receptor-mediated endocytosis and degradation of low-density lipoproteins

Receptor-mediated endocytosis of low-density lipoproteins, their transport within endosomes, and subsequent degradation in lysosomes are essential components of the molecular system for cholesterol homeostasis in vertebrate cells. The system under study is also an example of clathrin-mediated endocytosis, a possible way of cell communication with the environment. Construction of a detailed mathematical model of this system would allow comprehensive study of mechanisms and kinetics of molecular processes and evaluation of the effect of various mutations, disorders, and environmental changes on the system operation. Receptor-mediated endocytosis of low-density lipoprotein particles and their subsequent degradation in the cell have been modeled. A network of mono-and bimolecular reactions best describing the system has been proposed. The results of calculation of kinetic parameters of the molecular system obtained with the model are in agreement with experimental evidence.