Transition Metal Tunes Molecular Self-Assembly in Living Cells for Controlling Cell-Cell Crosstalk

Area of Science:

• Bioconjugation Chemistry
• Catalysis
• Cell Biology

Background:

• Precise control over peptide self-assembly in living systems is challenging.
• Abiotic catalysts offer potential for controlled molecular transformations within cells.
• Targeting specific cellular components like membranes is crucial for localized reactions.

Purpose of the Study:

• To develop a cell-compatible Ruthenium (Ru) catalyst for precise peptide self-assembly in living cells.
• To functionalize cell surfaces for targeted catalytic activity.
• To enable detection of molecular transfer between cells.

Main Methods:

• Engineering cell-compatible Ru catalysts with membrane-affinity groups.
• Functionalizing mammalian cell surfaces with the Ru catalyst.
• Utilizing olefin metathesis for *in situ* peptide self-assembly.
• Orthogonal labeling of CD8+ T cells and cancer cells.

Main Results:

• Demonstrated precise tuning of peptide self-assembly within living cells.
• Successfully targeted and anchored Ru catalysts to cell membranes.
• Enabled *in situ* peptide self-assembly via olefin metathesis.
• Showcased detection of molecular transfer from cancer to immune cells.

Conclusions:

• A robust and versatile strategy for harnessing cell-compatible transition metal catalysts is presented.
• This work provides a general approach for generating artificial peptide structures using abiotic catalysts in living cells.
• The technology allows for precise control and detection of molecular events at the cellular level.