Transmembrane signaling by a synthetic receptor in artificial cells

Abstract

Signal transduction across biological membranes is among the most important evolutionary achievements. Herein, for the design of artificial cells, we engineer fully synthetic receptors with the capacity of transmembrane signaling, using tools of chemistry. Our receptors exhibit similarity with their natural counterparts in having an exofacial ligand for signal capture, being membrane anchored, and featuring a releasable messenger molecule that performs enzyme activation as a downstream signaling event. The main difference from natural receptors is the mechanism of signal transduction, which is achieved using a self-immolative linker. The receptor scaffold is modular and can readily be re-designed to respond to diverse activation signals including biological or chemical stimuli. We demonstrate an artificial signaling cascade that achieves transmembrane enzyme activation, a hallmark of natural signaling receptors. Results of this work are relevant for engineering responsive artificial cells and interfacing them and/or biological counterparts in co-cultures.

Multicompartment Synthetic Vesicles for Artificial Cell Applications

“…This capability opens up numerous applications, including targeted drug delivery systems that respond to specific signals within the body and biosensors capable of imaging . In the pursuit of mimicking these intricate biological processes, artificial cell research has made significant strides, particularly in the development of multicompartment vesicles. , Compared to single compartmentalization, multicompartmentalization allows for spatiotemporal control over complex reactions, such as signal amplification or noise filtering . Therefore, understanding and replicating the spatiotemporal aspects of signal transduction in multicompartmentalized artificial cells not only advances our knowledge of basic biological processes but also facilitates the development of more sophisticated synthetic systems in diverse biomedical and biotechnological applications.…”

Artificial cells for in vivo biomedical applications through red blood cell biomimicry

“…What is more, when these biological units are exploited in non-conventional ways or when non-biological units are integrated, additional interesting functions can be integrated 198 . Examples of this include DNA origami nanopores 199 , transmembrane signal transducers built from synthetic chemicals 200 – 202 , magnetotactic behaviour endowed by encapsulated magnetic nanoparticles 203 and photo-inducible release enabled by photopolymerisable lipids 204 . In the following sections, some of these extra potential functionalities are highlighted.…”

Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells

“…The highest achievement of our prior reports was the artificial receptor-mediated transmembrane activation of a chemical zymogen in the void of a liposome, a simplified syncell. [15] In this work, we engineer syncells in which artificial signaling culminates in the activation of transcription. To achieve this, we developed chemical zymogens for the creatine kinase and for the T7 polymerase.…”

“…In pursuit of syncells with adaptive responsive behavior, we turned from the challenging implementation of natural signaling to the engineering of artificial signaling pathways. This approach required the development of both, artificial receptors for transmembrane signaling [ 15 ] and artificial enzyme activation pathways, [ 16 ] for downstream intracellular signaling. To this end, we developed transmembrane signaling using tools of organic chemistry whereby exofacial receptor activation resulted in the release of a secondary messenger to the interior of a syncell.…”