Figure 1. Computational model of autocrine signaling accurately predicts ligand capture differences between AREG and HB-EGF.

(a) Schematic of computational model that incorporates receptor trafficking combined with the proteolytic release, spatial diffusion, and receptor-mediated capture of growth factor ligands. (b) Ligand capture depends on ligand-receptor binding affinity, computationally modeled and represented here as the cumulative fraction of proteolytically released ligand that is captured by EGFR over the course of 24 h. (c) The computational model accurately predicts that HB-EGF is captured at higher levels compared to AREG. The fraction of bulk free ligand, equivalent to (1 - [fraction ligand capture]), was experimentally measured by taking the ratio of supernatant ligand concentrations after 24 h with or without the EGFR blocking antibody, mAb225 (n = 2 ± SEM).