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Modifying self-assembled peptide cages to control internalization into mammalian cells

Research output: Contribution to journalLetter

Original languageEnglish
JournalNano Letters
DateAccepted/In press - 3 Aug 2018
DatePublished (current) - 7 Aug 2018


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.

Keywords: cellular internalization; coiled coil; de novo peptide; nanoparticle; self-assembly

    Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

    Research areas

  • Synthetic Biology

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via ACS at Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 610 KB, PDF document


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