Engineering a Transmembrane Receptor for Coacervate-Based Artificial Cells

Area of Science:

• Biochemistry
• Synthetic Biology
• Materials Science

Background:

• Cell-surface receptors are crucial for cellular communication and response to stimuli.
• Mimicking membrane-mediated signaling in artificial cells is a growing area of interest for synthetic biology.
• Artificial cells offer a platform to study and engineer biological processes.

Purpose of the Study:

• To engineer a modular transmembrane receptor for synthetic signal transduction in artificial cells.
• To create a system that mimics natural cell-surface receptor function using synthetic components.
• To demonstrate a method for controlled signal activation and output in a synthetic system.

Main Methods:

• Engineered a heterodimerizing receptor with coiled-coil interactions and a transmembrane domain.
• Utilized elastin-like polypeptide (ELP) for membrane insertion and stability in copolymer membranes.
• Fused receptor subunits to split luciferase domains for bioluminescence-based signal detection.
• Assembled proteins into copolymer-membrane-decorated coacervates.

Main Results:

• Successfully inserted engineered proteins into artificial cell membranes, with insertion dependent on ELP sequence.
• Demonstrated retained protein diffusivity within the synthetic membrane.
• Achieved dose-dependent receptor activation upon addition of a soluble ditopic ligand.
• Observed a 5-fold increase in receptor activation, indicated by bioluminescence.

Conclusions:

• Developed a modular synthetic transmembrane receptor system for signal transduction in artificial cells.
• The engineered receptor successfully mimics natural cell signaling pathways.
• This modular platform holds potential for creating diverse synthetic receptors with tunable sensing and output functionalities.