title: Spatial control of membrane receptor function using ligand nanocalipers.
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.
authors.affiliation: 1] Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. [2].
authors.forename: Alan
authors.initials: A
authors.lastname: Shaw
authors.affiliation: 1] Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. [2].
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lundin
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Petrova
authors.affiliation: Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fördős
authors.affiliation: Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Benson
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Amin
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Herland
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Andries
authors.initials: A
authors.lastname: Blokzijl
authors.affiliation: 1] Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. [2].
authors.forename: Björn
authors.initials: B
authors.lastname: Högberg
authors.affiliation: 1] Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. [2].
authors.forename: Ana I
authors.initials: AI
authors.lastname: Teixeira
mesh_terms: D004705:Endocytosis; D008024:Ligands; D036103:Nanotechnology; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface