We present 2D model of low density lipoprotein (ldl) receptor-mediated endocytosis, intracellular transport and degradation to cholesterol combined with simulation of cellular microtubular transport system self-organization. Our aim was to describe spatial specificity of receptor-mediated endocytic pathway and investigate the role of dynamic nature of intracellular transport network.

The model consists of two coupled blocks. The first one describes dynamics of microtubule network and it is implemented by direct simulation of individual microtubule behavior. The second one is a system of partial differential equations describing spatial densities of different substances, such as ldl, ldl-receptors and cholesterol.

Using microtubule block of the model we have investigated basic properties of microtubule network as a transport facility such as adaptation ability, time of network reorganization and efficacy of network configuration. As a result we have derived trade-offs between significant traits of intracellular network. We are currently analyzing how transport network organization principles influence ldl metabolism.

In order to validate the model we have modeled experiments on receptor-mediated endocytosis in fibroblasts provided by Brown and Goldstein [1] and obtained similar behavior of substance densities.

References

[1] Brown M. S., Goldstein J. L. Receptor-mediated endocytosis: insights from the lipoprotein receptor system // Proceedings of the National Academy of Sciences, v. 76, N.7, p. 3330-3337, 1979.