Suh Kevin, Thornton Richard H, Nguyen Long, Farahani Payam E, Cohen Daniel J, Toettcher Jared E
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA.
Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell Syst. 2025 Mar 19;16(3):101203. doi: 10.1016/j.cels.2025.101203. Epub 2025 Mar 3.
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.
受体酪氨酸激酶（RTKs）在协调单细胞和组织尺度上的细胞运动中发挥着关键作用。用于控制RTKs及其下游信号通路的光遗传学工具的最新进展表明，这些反应可能适合基于工程的控制，以塑造组织的形状和功能。在这里，我们报告一种光控表皮生长因子（EGF）受体（OptoEGFR）可用于上皮细胞，以精确、可编程地控制远距离组织运动。我们表明，在表达OptoEGFR的组织中，光可以驱动毫米级的细胞重排，使内部区域致密化或在组织边缘产生快速生长。光控组织运动主要由磷酸肌醇3激酶（PI3K）信号传导驱动，而不是像在其他RTK驱动的迁移情况下那样由可扩散配体、组织收缩性或ERK激酶信号传导驱动。我们的研究表明，合成的、光控的RTKs可以作为一个强大的平台，用于控制细胞位置和密度，以实现多种应用，包括伤口愈合和组织形态发生。
