Intercellular communication between artificial cells by allosteric amplification of a molecular signal

Bastiaan C Buddingh',Janneke Elzinga,Jan C M Van Hest

doi:10.1038/s41467-020-15482-8

Bastiaan C Buddingh', Janneke Elzinga + Show 1 more

Open Access

https://doi.org/10.1038/s41467-020-15482-8

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Abstract

Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization. Various cell mimics have been developed to establish fundamental engineering principles for the construction of artificial cells displaying cell-like organization, behaviour and complexity. However, collective phenomena, although of great importance for a better understanding of life-like behaviour, are underexplored. Here, we construct collectives of giant vesicles that can communicate with each other through diffusing chemical signals that are recognized and processed by synthetic enzymatic cascades. Similar to biological cells, the Receiver vesicles can transduce a weak signal originating from Sender vesicles into a strong response by virtue of a signal amplification step, which facilitates the propagation of signals over long distances within the artificial cell consortia. This design advances the development of interconnected artificial cells that can exchange metabolic and positional information to coordinate their higher-order organization.

Highlights

Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization
Intercellular communication is critical to coordinate the behaviour of individual cells in multicellular communities, whether in multicellular organisms that use signalling to organize, synchronize and differentiate their specialized tissues[3], or in consortia of prokaryotes that control their behaviour based on the total population density[4]
The collective behaviour that can be generated is becoming increasingly complex with signalling circuits that can program feedback loops[13,36], amplification and logic tasks[13] and differentiation[36,38,39], most systems rely on cell-free protein expression[36,38] or DNA-strand displacement circuits[13] rather than chemical signals based on small molecules and proteinbased signal processing that is more reminiscent of natural signalling pathways

Summary

Introduction

Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization. The Receiver vesicles can transduce a weak signal originating from Sender vesicles into a strong response by virtue of a signal amplification step, which facilitates the propagation of signals over long distances within the artificial cell consortia This design advances the development of interconnected artificial cells that can exchange metabolic and positional information to coordinate their higher-order organization. The potential of artificial cells to develop new technologies based on biochemical information processing was explicitly put forward several years ago[19], and since several hybrid communication systems between artificial cells and biological cells have been developed These typically relied on passive diffusion of the signalling molecule over the synthetic membrane, and harnessed the biological cell’s resources to transduce a signal into the expression of a reporter gene[20,21,22,23,24]. Like endocrine signalling by hormones, rely on signal amplification to translate the stochastic stimulation elicited by dilute molecular messengers into a strong, amplified intracellular response[5,40]

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