Large-scale control over collective cell migration using light-activated epidermal growth factor receptors

  • Cell Syst. 2025 Mar 19;16(3):101203. doi: 10.1016/j.cels.2025.101203.
Kevin Suh  1 ,  Richard H Thornton  2 ,  Long Nguyen  3 ,  Payam E Farahani  4 ,  Daniel J Cohen  5 ,  Jared E Toettcher  6
Affiliations
  • 1. Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA.
  • 2. Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
  • 3. Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA.
  • 4. Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
  • 5. Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA; Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544, USA. Electronic address: [email protected].
  • 6. Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: [email protected].
PMID: 40037348 DOI: 10.1016/j.cels.2025.101203
Abstract

Receptor Tyrosine Kinases (RTKs) play key roles in coordinating cell movement at both single-cell and tissue scales. The recent development of optogenetic tools for controlling RTKs and their downstream signaling pathways suggests that these responses may be amenable to engineering-based control for sculpting tissue shape and function. Here, we report that a light-controlled epidermal growth factor (EGF) receptor (OptoEGFR) can be deployed in epithelial cells for precise, programmable control of long-range tissue movements. We show that in OptoEGFR-expressing tissues, light can drive millimeter-scale cell rearrangements to densify interior regions or produce rapid outgrowth at tissue edges. Light-controlled tissue movements are driven primarily by phosphoinositide 3-kinase (PI3K) signaling, rather than diffusible ligands, tissue contractility, or ERK kinase signaling as seen in Other RTK-driven migration contexts. Our study suggests that synthetic, light-controlled RTKs could serve as a powerful platform for controlling cell positions and densities for diverse applications, including wound healing and tissue morphogenesis.

Keywords
collective cell migration; epidermal growth factor receptor; optogenetics; tissue mechanics.
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