Surface-Patterned DNA Origami Rulers Reveal Nanoscale Distance Dependency of the Epidermal Growth Factor Receptor Activation.
Ivy MayerTina KarimianKlavdiya GordiyenkoAlessandro AngelinRavi KumarMichael HirtzRalf MikutMarkus ReischlJohannes StegmaierLu ZhouRui MaGerd Ulrich NienhausKersten S RabePeter LanzerstorferCarmen M DomínguezChristof M NiemeyerPublished in: Nano letters (2024)
The nanoscale arrangement of ligands can have a major effect on the activation of membrane receptor proteins and thus cellular communication mechanisms. Here we report on the technological development and use of tailored DNA origami-based molecular rulers to fabricate "Multiscale Origami Structures As Interface for Cells" (MOSAIC), to enable the systematic investigation of the effect of the nanoscale spacing of epidermal growth factor (EGF) ligands on the activation of the EGF receptor (EGFR). MOSAIC-based analyses revealed that EGF distances of about 30-40 nm led to the highest response in EGFR activation of adherent MCF7 and Hela cells. Our study emphasizes the significance of DNA-based platforms for the detailed investigation of the molecular mechanisms of cellular signaling cascades.
Keyphrases
- growth factor
- epidermal growth factor receptor
- tyrosine kinase
- induced apoptosis
- single molecule
- cell cycle arrest
- small cell lung cancer
- circulating tumor
- advanced non small cell lung cancer
- cell free
- atomic force microscopy
- cell death
- single cell
- high resolution
- gene expression
- endoplasmic reticulum stress
- signaling pathway
- breast cancer cells
- mass spectrometry
- genome wide
- nucleic acid
- dna methylation