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New Real‑Time Imaging Technique Reveals Dynamic Interactions Among Cancer Receptors

Sam Peng, PhD, Core Institute Member, Assistant Professor of Chemistry, Broad Institute of MIT and Harvard

Cancer‑driving receptors on the cell surface constantly move, pair, and reorganize, but scientists have lacked a way to watch these behaviors unfold in real time. Researchers in Sam Peng’s lab at MIT and the Broad Institute have now developed a new imaging technique that overcomes this barrier, enabling long‑duration observation of how cancer‑related receptors interact in living cells.

Published in Cell, the study focuses on the ErbB family of receptors—including EGFR, HER2, and HER3—which play central roles in cancers such as lung and breast cancer. Understanding how these receptors assemble and signal has been limited by the short lifespan of conventional fluorescent probes, which fade within seconds, preventing continuous tracking.

To address this, the Peng team developed highly stable upconverting nanoparticles that serve as long-lasting molecular beacons, enabling researchers to track receptor movements and interactions for more than 15 minutes. This extended window revealed behaviors that were previously inaccessible. For example, HER3 was found to form inactive self‑pairs that appear to act as a molecular reservoir, reducing its availability for signaling. The team also observed that cancer‑associated mutations—particularly in EGFR—promote unusually stable receptor pairing even without activating ligands, generating persistent growth signals.

By providing a time‑resolved view of how mutations alter receptor interactions on the cell surface, this new technique offers a clearer mechanistic picture of dysregulated signaling in cancer. It may also inform the development of more precise cancer‑focused therapeutic and drug‑screening strategies.

(Left) 16.7-minute continuous tracking of HaloTag-EGFRs at the bottom membrane of a live U2OS cell, incubated with 100 nM EGF. Long-term single-molecule trajectory of one receptor is shown in yellow. (Right) Interaction network between EGFR, HER2 and HER3, characterized by their dimer lifetimes, τ99%. The thickness of each arrow represents dimer stability. Stabilization of dimers by different ligands are also shown.

Read the full article in Cell here.