Competition for shared downstream signaling molecules establishes indirect negative feedback between EGFR and EphA2.

Cells sense a variety of extracellular growth factors and signaling molecules through numerous distinct receptor tyrosine kinases (RTKs) on the cell surface. In many cases, the same intracellular signaling molecules interact with more than one type of RTK. How signals from different RTKs retain the identity of the triggering receptor and how (or if) different receptors may synergize or compete remain largely unknown. Here we utilize an experimental strategy, combining microscale patterning and single-molecule imaging, to measure the competition between ephrin-A1:EphA2 and epidermal growth factor (EGF):EGF receptor (EGFR) ligand-receptor complexes for the shared downstream signaling molecules, Grb2 and SOS. The results reveal a distinct hierarchy, in which newly formed EGF:EGFR complexes outcompete ephrin-A1:EphA2 for Grb2 and SOS, revealing a type of negative crosstalk interaction fundamentally controlled by chemical mass action and protein copy number limitations.

Three-dimensional quantitative microwave imaging of realistic numerical breast phantoms using Huber regularization.

Breast tumor detection with microwaves is based on the difference in dielectric properties between normal and malignant tissues. The complex permittivity reconstruction of inhomogeneous dielectric biological tissues from microwave scattering is a nonlinear, ill-posed inverse problem. We proposed to use the Huber regularization in our previous work where some preliminary results for piecewise constant objects were shown. In this paper, we employ the Huber function as regularization in the even more challenging 3D piecewise continuous case of a realistic numerical breast phantom. The resulting reconstructions of complex permittivity profiles indicate potential for biomedical imaging.