Programmable On-Chip Artificial Cell Producing Post-Translationally Modified Ubiquitinated Protein

Area of Science:

• Synthetic biology
• Biotechnology
• Cellular engineering

Background:

• Intracellular microcompartments in nature enable complex cellular processes.
• Artificial cells aim to replicate this compartmentalization for biomolecule production.
• Existing artificial cells struggle to sequentially control central dogma activities.

Purpose of the Study:

• To design and fabricate an artificial cell-on-a-chip with hierarchical compartments.
• To enable sequential control over transcription, translation, and post-translational modifications.
• To produce complex, modified biomolecules, such as disease-associated proteins.

Main Methods:

• Development of a microfluidic 'cell-on-a-chip' platform.
• Integration of hierarchical compartments for sequential processing.
• Linking compartments via channels for product transport.
• Demonstration of DNA-to-purified-modified-protein synthesis.

Main Results:

• Successful fabrication of a hierarchical compartmentalized artificial cell system.
• Demonstrated sequential control of transcription, translation, and post-translational modifications.
• Produced the fully ubiquitinated form of α-synuclein, linked to Parkinson's disease, from DNA in a single device.

Conclusions:

• The artificial cell-on-a-chip platform allows for tightly controlled, sequential execution of central dogma activities.
• This system enables the direct production of purified, modified proteins.
• The platform holds potential for synthesizing complex targets, studying molecular mechanisms, and engineering protein-based therapeutics.