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Nat Methods. 2014 Aug;11(8):841-6. doi: 10.1038/nmeth.3025. Epub 2014 Jul 6.

Spatial control of membrane receptor function using ligand nanocalipers.

Author information

1
1] Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. [2].
2
1] Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. [2].
3
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
4
Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
5
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Abstract

The spatial organization of membrane-bound ligands is thought to regulate receptor-mediated signaling. However, direct regulation of receptor function by nanoscale distribution of ligands has not yet been demonstrated, to our knowledge. We developed rationally designed DNA origami nanostructures modified with ligands at well-defined positions. Using these 'nanocalipers' to present ephrin ligands, we showed that the nanoscale spacing of ephrin-A5 directs the levels of EphA2 receptor activation in human breast cancer cells. Furthermore, we found that the nanoscale distribution of ephrin-A5 regulates the invasive properties of breast cancer cells. Our ligand nanocaliper approach has the potential to provide insight into the roles of ligand nanoscale spatial distribution in membrane receptor-mediated signaling.

PMID:
24997862
DOI:
10.1038/nmeth.3025
[Indexed for MEDLINE]
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