Fig. 6. A series of molecular mechanisms for cetuximab induced EGFR endocytosis. (A) The illustrations for a proposed model to account for a series of molecular mechanisms of cetuximab induced EGFR endocytosis on a living cell membrane. Each kinetic parameter at 37 °C was estimated from a set of rate equations for the sequential reaction with the cooperativity model shown in Fig. 4C. Cetuximab binds to monomeric EGFR with a first-order reaction, followed by a high-order rate law reaction for an unknown intermediate state that may involve clathrin dependent EGFR oligomerization. Finally, cetuximab bound EGFR in the unknown intermediate state is trapped in a CCP with a first-order reaction for clathrin mediated endocytosis. (B) EGFR internalization induced by cetuximab treated for 12 h on cell lines with different surface expression levels of EGFR at 37 °C. The proposed model (A) fits the experimental data (red line).
