Published online in Nature Biotechnology last week, a multi-national team from Switzerland, Germany and France demonstrated the first example of rationally designed, two-way communication between mammalian cells (Source). While the microbiologist might scoff at this and point to any of the glut of literature describing synthetically design genetic circuits and phenotypic responses achieved in bacterial and yeast systems, the mammalian cell poses a significantly greater challenge. In the Letters publication, Bacchus et al. describe the engineering of “sender,” “processer” and “receiver” cells (all HEK-293 cells, a favorite for mammalian genetic engineers due to the ease of introducing foreign DNA) to exchange a variety of signaling molecules (including L-tryptophan, VEGF and acetaldehyde) in order to trigger specific, and pre-determined phenotypic responses.
This is huge.
This is the first time that mammalian cells have been rationally designed to mimic natural behavior in order to produce a specifically desired response. Even more impressively, they didn’t leave their demonstration at just a simple signaling exchange – they showed a realistic, biologically relevant phenotypic response! The authors designed an experiment wherein a co-culture of cells designed to express and respond to different stimuli simulated the production and maturation of blood vessels. Using the vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), the authors observed that their system reproduced the characteristic transient permeability and tightening of endothelial layers which are critically important to the growth of blood vessels.
The authors emphasize the important point that, in contrast to bacteria and yeast, multicellular organisms are composed of specialized cell populations that tightly coordinate their physiology by intercellular communication. This article represents the first reverse-engineering of this intercellular communication, and in particular the first to reproduce a realistic biological phenomena. This development can provide two important opportunities for the research community: first, it can provide the tools to dissect important communication pathways and finely understand the nuances of these communications, much in the same way that recombinant DNA technology allowed us to do for gene networks; and second it provides the opportunity to design more biocompatible implants capable of communicating and interfacing with our natural physiology.
Catch the article in the link below!
- Bacchus, W. et al. Synthetic two-way communication between mammalian cells. Nature Biotechnology (2012).doi:10.1038/nbt.2351 (Source)