DNA-Mediated Protein Shuttling between Coacervate-Based Artificial Cells

The regulation of protein uptake and secretion is crucial for (inter)cellular signaling. Mimicking these molecular events is essential when engineering synthetic cellular systems. A first step towards achieving this goal is obtaining control over the uptake and release of proteins from synthetic cells in response to an external trigger. Herein, we have developed an artificial cell that sequesters and releases proteinaceous cargo upon addition of a coded chemical signal: single-stranded DNA oligos (ssDNA) were employed to independently control the localization of a set of three different ssDNA-modified proteins. The molecular coded signal allows for multiple iterations of triggered uptake and release, regulation of the amount and rate of protein release and the sequential release of the three different proteins. This signaling concept was furthermore used to directionally transfer a protein between two artificial cell populations, providing novel directions for engineering lifelike communication pathways inside higher order (proto)cellular structures.

Automated summary

Regulating the uptake and release of proteins is crucial for engineering synthetic cellular systems. This study presents the development of an artificial cell that can sequester and release protein cargo in response to a coded chemical signal. The molecular coded signal allows for multiple iterations of triggered uptake and release, fine control over the amount and rate of protein release, and sequential release of different proteins. Additionally, this signaling concept enables directional transfer of proteins between artificial cell populations, suggesting new possibilities for engineering lifelike communication pathways.