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

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.

Recent Progress of DNA Nanostructures on Amphiphilic Membranes

“…[122] Replacing the chain with a controlled key chain or increasing the temperature reopened the channel and removed the small molecular cargo from the vesicle container. By using this small DNA nanopore with the gating function, Tan et al designed a DNA-based artificial molecular signaling system [132] in a closed microenvironment of huge vesicles from living cells. First, they established a DNA nanoretainer driven by adenosine triphosphate (ATP), in which the DNA blocker strand contains ATP aptamer sequences that could block DNA nanopores.…”

Recent Advances of DNA Nanostructure‐Based Cell Membrane Engineering

“…Because of the excellent addressability and programmability of DNA nanostructures, recently, especially after 2010, there is an increasing number of researches related to DNA nanostructures in imitating channel proteins. [ 18,61,63,101,102,106,109,115–117 ]…”

“…Adapted under the terms of the CC BY 4.0 License. [ 116 ] Copyright 2020, The Authors. Published by Springer Nature.…”

“…In 2020, Tan and co‐workers designed a set of DNA‐based artificial molecular signaling networks. [ 116 ] Using giant vesicles derived from living cells as a restricted microenvironment, they constructed an ATP‐driven DNA artificial channel and a signal network system in the lipid vesicles. The signal network system could initiate a series of downstream reactions in turn, realizing the reception, conduction, and response functions (Figure 7e).…”

Microfluidic platform enables tailored translocation and reaction cascades in nanoliter droplet networks

“…Many pathways require multiple steps in different organelles, translocation of intermediate products between organelles, and signaling cascades to enable the cell to sense the environment or relay information between different cellular regions. In this regard, major achievements were presented recently, reporting the realization of multistep reactions 4,5 , genetic circuits [8][9][10] , controlled division 11 or communication pathways across membranes [12][13][14] in artificial cell models.…”