Engineered cell-cell communication via DNA messaging.

Monica E Ortiz,Drew Endy

doi:10.1186/1754-1611-6-16

Abstract

BackgroundEvolution has selected for organisms that benefit from genetically encoded cell-cell communication. Engineers have begun to repurpose elements of natural communication systems to realize programmed pattern formation and coordinate other population-level behaviors. However, existing engineered systems rely on system-specific small molecules to send molecular messages among cells. Thus, the information transmission capacity of current engineered biological communication systems is physically limited by specific biomolecules that are capable of sending only a single message, typically “regulate transcription.”ResultsWe have engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. We demonstrate the decoupling of messages from a common communication channel via the autonomous transmission of various arbitrary genetic messages. Further, we increase the range of engineered DNA messaging across semisolid media by linking message transmission or receipt to active cellular chemotaxis.ConclusionsWe demonstrate decoupling of a communication channel from message transmission within engineered biological systems via the autonomous targeted transduction of user-specified heterologous DNA messages. We also demonstrate that bacteriophage M13 particle production and message transduction occurs among chemotactic bacteria. We use chemotaxis to improve the range of DNA messaging, increasing both transmission distance and communication bit rates relative to existing small molecule-based communication systems. We postulate that integration of different engineered cell-cell communication platforms will allow for more complex spatial programming of dynamic cellular consortia.

Highlights

Evolution has selected for organisms that benefit from genetically encoded cell-cell communication
Longer range messaging via chemotaxis We demonstrated that the range of M13-based DNA messaging can be increased using bacterial chemotaxis
We observed that over 33% of receiver cells were transduced via M13-mediated messaging within a semisolid medium across a ~7 centimeter gap bridged by chemotaxis of sender and receiver cells, again as observed by message readout within receivers prior to selection for message receipt (Figure 4a-b)

Summary

Introduction

Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. Engineers have begun to repurpose elements of natural communication systems to realize programmed pattern formation and coordinate other population-level behaviors. Existing engineered systems rely on system-specific small molecules to send molecular messages among cells. The information transmission capacity of current engineered biological communication systems is physically limited by specific biomolecules that are capable of sending only a single message, typically “regulate transcription.”. Other engineering disciplines have recognized the importance of understanding and programming systems across both space and time, and have even begun to map such work to biological substrates. The resulting space-time programming frameworks enable both the analysis and forward engineering of complex systems capable of programmed pattern formation and restoration (i.e., “healing”) in the presence of noise or damage [3,4,5]. Much improved cell-cell communication platforms are needed for scientists and engineers to practically benefit from and advance such research

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Conclusion