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De novo design of an intercellular signaling toolbox for multi-channel cell-cell communication and biological computation.

Abstract：

:Intercellular signaling is indispensable for single cells to form complex biological structures, such as biofilms, tissues and organs. The genetic tools available for engineering intercellular signaling, however, are quite limited. Here we exploit the chemical diversity of biological small molecules to de novo design a genetic toolbox for high-performance, multi-channel cell-cell communications and biological computations. By biosynthetic pathway design for signal molecules, rational engineering of sensing promoters and directed evolution of sensing transcription factors, we obtain six cell-cell signaling channels in bacteria with orthogonality far exceeding the conventional quorum sensing systems and successfully transfer some of them into yeast and human cells. For demonstration, they are applied in cell consortia to generate bacterial colony-patterns using up to four signaling channels simultaneously and to implement distributed bio-computation containing seven different strains as basic units. This intercellular signaling toolbox paves the way for engineering complex multicellularity including artificial ecosystems and smart tissues.

journal_name

Nat Commun

journal_title

Nature communications

authors

Du P,Zhao H,Zhang H,Wang R,Huang J,Tian Y,Luo X,Luo X,Wang M,Xiang Y,Qian L,Chen Y,Tao Y,Lou C

doi

10.1038/s41467-020-17993-w

subject

Has Abstract

pub_date

2020-08-24 00:00:00

pages

4226

issue

1

issn

2041-1723

pii

10.1038/s41467-020-17993-w

journal_volume

11

pub_type

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