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Fluorescent Leakage Assay to Investigate Membrane Destabilization by Cell-Penetrating Peptide
Published on: December 19, 2020
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Polyfluoroalkyl-Tagged Cell-Penetrating Peptide-Additives Enhance Intracellular Protein Delivery via Sustained
Sarah Hansen1,2, Hana Zupan3, Ferhat Mutlu4
1Leibniz-Forschungsinstitut Für Molekulare Pharmakologie (FMP), Berlin, Germany.
Angewandte Chemie (International Ed. in English)
|April 15, 2026
Summary
New polyfluoroalkyl-tagged cell-penetrating peptides (CPPs) enhance protein delivery into cells. These CPP-additives show sustained membrane interaction and improved delivery without toxicity, offering a promising tool for intracellular protein delivery.
Area of Science:
- Biochemistry
- Cell Biology
- Materials Science
Background:
- Cell-penetrating peptides (CPPs) are crucial for intracellular delivery.
- Sustained membrane association is key for efficient CPP-mediated protein delivery.
Purpose of the Study:
- To develop novel CPP-additives for enhanced intracellular protein delivery.
- To investigate the role of polyfluoroalkyl tags in CPP membrane interactions and delivery efficiency.
Main Methods:
- Synthesis and application of polyfluoroalkyl-tagged polyarginine peptides.
- Live-cell time-lapse fluorescence imaging.
- Surface-enhanced infrared absorption spectroscopy (SEIRAS) with lipid bilayers.
- Molecular dynamics simulations.
Main Results:
- CPP-additives with 11-13 fluorine atoms enhanced protein delivery over 2-fold at 2.5 µM without cytotoxicity.
- A 13-fluorine atom CPP-additive demonstrated prolonged membrane association (>5 min) and rapid internalization (<10 min).
- SEIRAS and simulations revealed monomeric insertion into lipid bilayers without tag aggregation.
Conclusions:
- Polyfluoroalkyl-tagged CPP-additives are effective, non-cytotoxic vectors for intracellular protein delivery.
- The fluorous tags enhance CPPs' membrane interaction and insertion mechanisms.
- These findings provide mechanistic insights into CPP-lipid bilayer interactions for improved delivery strategies.
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