Synthetic cells with self-activating optogenetic proteins communicate with natural cells

Omer Adir, Mia R. Albalak, Ravit Abel, Lucien E. Weiss, Gal Chen, Amit Gruber, Oskar Staufer, Yaniv Kurman, Ido Kaminer, Jeny Shklover, Janna Shainsky-Roitman, Ilia Platzman, Lior Gepstein, Yoav Shechtman, Benjamin A. Horwitz and Avi Schroeder ()
Additional contact information
Omer Adir: Technion
Mia R. Albalak: Technion
Ravit Abel: Technion
Lucien E. Weiss: Technion
Gal Chen: Technion
Amit Gruber: the Rappaport Faculty of Medicine and Research Institute, Technion
Oskar Staufer: Max Planck Institute for Medical Research
Yaniv Kurman: Technion
Ido Kaminer: Technion
Jeny Shklover: Technion
Janna Shainsky-Roitman: Technion
Ilia Platzman: Max Planck Institute for Medical Research
Lior Gepstein: the Rappaport Faculty of Medicine and Research Institute, Technion
Yoav Shechtman: Technion
Benjamin A. Horwitz: Technion - Israel Institute of Technology
Avi Schroeder: Technion

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Development of regulated cellular processes and signaling methods in synthetic cells is essential for their integration with living materials. Light is an attractive tool to achieve this, but the limited penetration depth into tissue of visible light restricts its usability for in-vivo applications. Here, we describe the design and implementation of bioluminescent intercellular and intracellular signaling mechanisms in synthetic cells, dismissing the need for an external light source. First, we engineer light generating SCs with an optimized lipid membrane and internal composition, to maximize luciferase expression levels and enable high-intensity emission. Next, we show these cells’ capacity to trigger bioprocesses in natural cells by initiating asexual sporulation of dark-grown mycelial cells of the fungus Trichoderma atroviride. Finally, we demonstrate regulated transcription and membrane recruitment in synthetic cells using bioluminescent intracellular signaling with self-activating fusion proteins. These functionalities pave the way for deploying synthetic cells as embeddable microscale light sources that are capable of controlling engineered processes inside tissues.

Date: 2022
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DOI: 10.1038/s41467-022-29871-8

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