title: Quantitative Analysis of Delta-like 1 Membrane Dynamics Elucidates the Role of Contact Geometry on Notch Signaling.
abstract: Notch signaling is ubiquitously used to coordinate differentiation between adjacent cells across metazoans. Whereas Notch pathway components have been studied extensively, the effect of membrane distribution and dynamics of Notch receptors and ligands remains poorly understood. It is also unclear how cellular morphology affects these distributions and, ultimately, the signaling between cells. Here, we combine live-cell imaging and mathematical modeling to address these questions. We use a FRAP-TIRF assay to measure the diffusion and endocytosis rates of Delta-like 1 (Dll1) in mammalian cells. We find large cell-to-cell variability in the diffusion coefficients of Dll1 measured in single cells within the same population. Using a simple reaction-diffusion model, we show how membrane dynamics and cell morphology affect cell-cell signaling. We find that differences in the diffusion coefficients, as observed experimentally, can dramatically affect signaling between cells. Together, these results elucidate how membrane dynamics and cellular geometry can affect cell-cell signaling.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Itzhak
authors.initials: I
authors.lastname: Khait
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Orsher
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Golan
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Udi
authors.initials: U
authors.lastname: Binshtok
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Nadav
authors.initials: N
authors.lastname: Gordon-Bar
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Amir-Zilberstein
authors.affiliation: Department of Biochemistry and Molecular Biology, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: davidsp@post.tau.ac.il.
authors.forename: David
authors.initials: D
authors.lastname: Sprinzak
mesh_terms: D002135:Calcium-Binding Proteins; D002450:Cell Communication; D002454:Cell Differentiation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch
keywords: Notch signaling; diffusion; membrane dynamics