Clustering of Death Receptor for Apoptosis Using Nanoscale Patterns of Peptides

ACS Nano. 2021 Jun 22;15(6):9614-9626. doi: 10.1021/acsnano.0c10104. Epub 2021 May 21.

Abstract

The nanoscale spatial organization of transmembrane tumor necrosis factor (TNF) receptors has been implicated in the regulation of cellular fate. Accordingly, molecular tools that can induce specific arrangements of these receptors on cell surfaces would give us an opportunity to study these effects in detail. To achieve this, we introduce DNA origami nanostructures that precisely scaffold the patterning of TNF-related apoptosis-inducing ligand-mimicking peptides at nanoscale level. Stimulating human breast cancer cells with these patterns, we find that around 5 nm is the critical interligand distance of hexagonally patterned peptides to induce death receptor clustering and a resulting apoptosis. We thus offer a strategy to reverse the non-efficacy of current ligand- and antibody-based methods for TNF superfamily activation.

Keywords: DNA origami; TRAIL-mimicking peptide; apoptosis; death receptor clustering; hexagonal pattern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cluster Analysis
  • Humans
  • Peptides
  • Receptors, TNF-Related Apoptosis-Inducing Ligand*
  • TNF-Related Apoptosis-Inducing Ligand*
  • Tumor Necrosis Factor-alpha

Substances

  • Peptides
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha