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
Original languageEnglish
JournalNano Letters
Publication statusPublished - 7 Aug 2018

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute


  • Synthetic Biology


Dive into the research topics of 'Modifying self-assembled peptide cages to control internalization into mammalian cells'. Together they form a unique fingerprint.

Cite this