Multiscale Monte Carlo study of epidermal growth factor receptor diffusion and dimerization
Date
2009
Authors
Journal Title
Journal ISSN
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Publisher
University of Delaware
Abstract
The ErbB family of receptors is dysregulated in a number of cancers, and the
signaling pathway of this receptor family is a critical target for several anti-cancer drugs.
Therefore, a detailed understanding of the mechanisms of receptors activation is critical.
However, despite a plethora of biochemical studies and single particle tracking
experiments, the early molecular mechanisms involving epidermal growth factor (EGF)
binding and EGF receptor (EGFR) dimerization are not as well understood. Due to the large
disparity of time and length scales involved in receptor dimerization reactions, we adapt the
coarse-grained Monte Carlo (CGMC) simulation framework to enable the simulation of in
vivo receptor diffusion and dimerization.
Using the CGMC method, spatial modeling of ligand-mediated membrane
receptor dimerization reaction dynamics was performed. Furthermore, the simulations
demonstrate the importance of spatial heterogeneity in membrane receptor localization.
Mathematical models, especially one that takes into account spatial heterogeneity, show
mechanistic understanding of receptor activation that may in turn enable improved future
cancer treatments.