Restoring intracellular homeostasis disrupted by synthetic nanoassemblies

Area of Science:

• Biotechnology
• Synthetic Biology
• Cellular Homeostasis

Background:

• Cells maintain homeostasis to survive but lack mechanisms to expel novel synthetic nanostructures.
• Synthetic nanostructures can disrupt cellular redox and energy balance.

Purpose of the Study:

• To establish crosstalk between supramolecular transformations and genetic responses for programmable nanoassembly influx-efflux cycles.
• To restore redox and energy homeostasis in bacterial cells using dynamic nanostructures.

Main Methods:

• Utilized a photosensitizer-peptide conjugate undergoing redox cycles and morphological transformations (nanofibers to nanoparticles).
• Engineered bacteria to express methionine sulfoxide (MetO) reductases in response to photo-oxidative stress.
• Demonstrated intracellular enzymatic reduction and expulsion of nanoparticles as nanofibers.

Main Results:

• Achieved programmable influx-efflux cycles of nanoassemblies in living bacterial cells.
• Successfully restored redox and energy homeostasis through the engineered pathway.
• Demonstrated reversible morphological transformations of peptide conjugates linked to cellular responses.

Conclusions:

• Established a novel interlinked network between dynamic supramolecular assemblies and cellular regulatory behaviors.
• Paved the way for programmable expulsion of synthetic nanostructures to maintain cellular homeostasis.
• Opened new avenues for nanomedicine and synthetic biology applications.