Quantitative Analysis of Delta-like 1 Membrane Dynamics Elucidates the Role of Contact Geometry on Notch Signaling
Quantitative Analysis of Delta-like 1 Membrane Dynamics Elucidates the Role of Contact Geometry on Notch Signaling
复制标题
DOI：
10.1016/j.celrep.2015.12.040
复制
发表时间：
2016-01-12
期刊：
影响因子：
8.8
通讯作者：
Sprinzak, David
中科院分区：
文献类型：
--
作者：
Khait, Itzhak;Orsher, Yuval;Sprinzak, David
Notch信号转导广泛用于协调多细胞动物中相邻细胞之间的分化。尽管Notch途径组分已被广泛研究，但Notch受体和配体的膜分布和动力学的影响仍然知之甚少。目前还不清楚细胞形态如何影响这些分布，并最终影响细胞之间的信号传导。在这里，我们结合联合收割机活细胞成像和数学建模来解决这些问题。我们使用FRAP-TIRF测定来测量Delta-like 1（Dll 1）在哺乳动物细胞中的扩散和内吞速率。我们发现大细胞间的差异，在同一人口内的单细胞中测得的Dll 1的扩散系数。使用一个简单的反应扩散模型，我们展示了膜动力学和细胞形态如何影响细胞-细胞信号。我们发现，扩散系数的差异，如实验所观察到的，可以显着影响细胞之间的信号。总之，这些结果阐明了膜动力学和细胞几何形状如何影响细胞-细胞信号传导。
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.