Recent developments in microscopy have led to revolutionary advances in our knowledge of the spatiotemporal dynamics of proteins in the plasma membrane of living cells and of heterogeneity of the plasma membrane. For example, spatial heterogeneities in the epidermal growth factor (EGF) receptor (EGFR) distribution in different domains of the plasma membrane are becoming increasingly evident. However, the influence of these heterogeneities on cellular signaling remains elusive despite uncontrolled receptor signaling being implicated in various forms of cancer. Herein, we suggest a reaction engineering, multiscale simulation framework, coined as model based bio-imaging informatics. This framework can fill in the scales' gap between various experimental methods and analyze the wealth of image informatics to unravel the influence of plasma membrane heterogeneities on the early events of the EGFR signaling, namely EGF binding and EGFR dimerization. An overarching conclusion arising from our work is that the plasma membrane hetero.-enei ties can strongly modulate the amount as well the mechanism of ligand-receptor binding. (c) 2007 Elsevier Ltd. All rights reserved.