Excited to share our work on ErbB receptors published today @CellCellPress! Using multicolor, photostable UCNPs, we perform long-term (>15 min) single-particle tracking of EGFR, HER2, and HER3, enabling direct visualization of dimerization in live cells. cell.com/cell/fulltext/S0092…

We show oncogenic EGFR mutations promote stable, ligand-independent dimerization. Unexpectedly, both HER2 and HER3 exhibit constitutive homodimerization, prompting a revised model for their activation mechanisms.

Dimer lifetimes follow a power-law. Confirming this requires a linear trend on a log-log plot over >2 orders of magnitude on both axes, which means measuring lifetimes beyond several minutes. UCNPs’ exceptional photostability now makes these rare long-lived events detectable.

HER2 mutations modestly enhance homodimer stability compared to EGFR mutations, while HER3 mutations destabilize homodimers, suggesting that HER3 homodimerization sequesters HER3 and limits heterodimerization with other receptors.