Multiscale Monte Carlo study of epidermal growth factor receptor diffusion and dimerization

Author(s)Collins, Stuart
Date Accessioned2010-08-05T22:18:18Z
Date Available2010-08-05T22:18:18Z
Publication Date2009
AbstractThe 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.en
AdvisorVlachos, Dionisios G.
DegreeM.C.E.
DepartmentUniversity of Delaware, Department of Chemical Engineering
URLhttp://udspace.udel.edu/handle/19716/5485
PublisherUniversity of Delawareen
dc.subject.lcshEpidermal growth factor -- Receptors
dc.subject.lcshMonte Carlo method
TitleMultiscale Monte Carlo study of epidermal growth factor receptor diffusion and dimerizationen
TypeThesisen
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