Controlled Supramolecular Assembly Inside Living Cells by Sequential Multistaged Chemical Reactions

Area of Science:

• Biochemistry
• Synthetic Biology
• Cell Biology

Background:

• Synthetic assembly within living cells offers novel chemical tools for controlling cellular behavior.
• Existing methods often lack modularity and intricate molecular recognition capabilities.

Purpose of the Study:

• To develop a simple, modular platform for in situ synthetic assembly inside living cells.
• To demonstrate the ability of tailored peptide sequences to direct intracellular architecture formation and cellular responses.

Main Methods:

• Utilized short bimodular peptide sequences designed for specific intracellular events.
• Investigated cellular uptake, transport, localization, and structural changes.
• Assessed programmed cell death via Annexin V binding.
• Explored coassembly of different peptide sequences for complex architectures.

Main Results:

• Demonstrated programmed assembly of fibrillar architectures within the intracellular environment.
• Confirmed induction of apoptosis (programmed cell death) mediated by peptide assembly.
• Achieved higher complexity assemblies, including intrinsically fluorescent architectures, through coassembly.
• Showcased the successful tailoring of peptide sequences for controlled intracellular events.

Conclusions:

• The in situ construction of architectures within cells provides a powerful strategy for directing cellular behavior.
• This platform enables the exploration of complex molecular recognition and rearrangement chemistry in a living system.
• The findings broaden the understanding of how structure formation impacts living systems and opens new avenues for synthetic biology.