DNA-based artificial molecular signaling system that mimics basic elements of reception and response

Ruizi Peng,Liujun Xu,Cheng Bi,Dan Wang,Yifan Lyu,Huijing Wang,Weihong Tan,Cheng Cui,Qiaoling Liu,Xiaobing Zhang,Chunhai Fan

doi:10.1038/s41467-020-14739-6

Abstract

In order to maintain tissue homeostasis, cells communicate with the outside environment by receiving molecular signals, transmitting them, and responding accordingly with signaling pathways. Thus, one key challenge in engineering molecular signaling systems involves the design and construction of different modules into a rationally integrated system that mimics the cascade of molecular events. Herein, we rationally design a DNA-based artificial molecular signaling system that uses the confined microenvironment of a giant vesicle, derived from a living cell. This system consists of two main components. First, we build an adenosine triphosphate (ATP)-driven DNA nanogatekeeper. Second, we encapsulate a signaling network in the biomimetic vesicle, consisting of distinct modules, able to sequentially initiate a series of downstream reactions playing the roles of reception, transduction and response. Operationally, in the presence of ATP, nanogatekeeper switches from the closed to open state. The open state then triggers the sequential activation of confined downstream signaling modules.

Highlights

In order to maintain tissue homeostasis, cells communicate with the outside environment by receiving molecular signals, transmitting them, and responding with signaling pathways
We have designed and constructed an artificial molecular signaling system (AMSsys), a rationally integrated system able to mimic the cascade of molecular events from signal reception to transduction and, response, all based on an isolated biomimetic giant vesicle
Ion channels are involved in many cellular processes in which an activated ion channel triggers a cascade of downstream reactions

Summary

Introduction

In order to maintain tissue homeostasis, cells communicate with the outside environment by receiving molecular signals, transmitting them, and responding with signaling pathways. This, in turn, activates our integrated giant plasma membrane vesicle (GPMV, Supplementary Table 1)-encapsulated signal switching network, consisting of distinct cell-signaling modules, to sequentially accomplish a series of cell-mimicking reactions involving reception, transduction and response. By rationally integrating DNA nanostructure and dynamic cascade networks into this biomimetic GPMV, we demonstrate that an artificial molecular signaling system can, process environmental cues and react with downstream signaling that mimics real cellular behavior. This system consists of two main components. A concurrent signal released from the feedback pathway switches nanogatekeeper back to the closed state after cellular response

Methods

Results

Conclusion