Journal
NANO LETTERS
Volume 18, Issue 9, Pages 5933-5937Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.8b02633
Keywords
de novo peptide; coiled coil; self-assembly; nanoparticle; cellular internalization
Categories
Funding
- BBSRC South West Doctoral Training Partnership
- BBSRC [BB/L010518/1, BBM002969/1, BB/J008990/1]
- ERC [340764]
- Royal Society Wolfson Research Merit Award [WM140008]
- BrisSynBio, a BBSRC/EPSRC [BB/L01386X/1]
- EPSRC [EP/K03927X/1]
- Medical Research Council
- Wolfson Foundation
- BBSRC [BB/J008990/1, BB/L010518/1, BB/L01386X/1] Funding Source: UKRI
- EPSRC [EP/K03927X/1] Funding Source: UKRI
- European Research Council (ERC) [340764] Funding Source: European Research Council (ERC)
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Nanoparticles can be used to transport a variety of biological cargoes into eukaryotic cells. Polypeptides provide a versatile material for constructing such systems. Previously, we have assembled nanoscale peptide cages (SAGEs) from de novo designed coiled-coil modules. Here, we show that the modules can be extended with short charged peptides to alter endocytosis of the assembled SAGE particles by cultured human cells in a tunable fashion. First, we find that the peptide extensions affect coiled-coil stability predictably: N-terminal polylysine and C-terminal polyglutamate tags are destabilizing; whereas, the reversed arrangements have little impact. Second, the cationic assembled particles are internalized faster and to greater extents by cells than the parent SAGEs. By contrast, anionic decorations markedly inhibit both aspects of uptake. These studies highlight how the modular SAGE system facilitates rational peptide design to fine-tune the bioactivity of nanoparticles, which should allow engineering of tailored cell-delivery vehicles.
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