Cellular Uptake of Phase-Separating Peptide Coacervates
Anastasia Shebanova1, Quentin Moana Perrin1, Kexin Zhu2
1Centre for Sustainable Materials, School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Avenue, Singapore, 637553, Singapore.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 30, 2024
Summary
Peptide coacervates efficiently deliver therapeutics but how they enter cells was unknown. This study reveals a novel uptake pathway combining macropinocytosis and phagocytosis features, crucial for enhancing drug delivery.
Area of Science:
- Biochemistry
- Cell Biology
- Materials Science
Background:
- Peptide coacervates are promising intracellular delivery vehicles for macromolecular therapeutics.
- Their mechanisms for crossing cellular membranes are not well understood.
Purpose of the Study:
- To elucidate the cellular uptake mechanisms of peptide coacervates.
- To identify key cellular processes involved in coacervate internalization.
Main Methods:
- Multimodal imaging
- Data analytics
- Biochemical inhibition assays
- Giant unilamellar vesicle experiments
- Electron microscopy
Main Results:
- Coacervate uptake follows a non-canonical pathway integrating macropinocytosis and phagocytosis features.
- Uptake involves actin cytoskeleton remodeling and filopodia-like protrusions.
- Coacervates attach to membranes in a charge- and cholesterol-dependent manner without breaching the lipid bilayer.
Conclusions:
- Peptide coacervates utilize a unique internalization mechanism combining fluid and particulate uptake characteristics.
- Understanding this mechanism can improve coacervate-based therapeutic delivery strategies.
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