Department of Physics, Harvard University, Cambridge, United States.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
Elife. 2020 Dec 4;9:e61771. doi: 10.7554/eLife.61771.
In biological contexts as diverse as development, apoptosis, and synthetic microbial consortia, collections of cells or subcellular components have been shown to overcome the slow signaling speed of simple diffusion by utilizing diffusive relays, in which the presence of one type of diffusible signaling molecule triggers participation in the emission of the same type of molecule. This collective effect gives rise to fast-traveling diffusive waves. Here, in the context of cell signaling, we show that system dimensionality - the shape of the extracellular medium and the distribution of cells within it - can dramatically affect the wave dynamics, but that these dynamics are insensitive to details of cellular activation. As an example, we show that neutrophil swarming experiments exhibit dynamical signatures consistent with the proposed signaling motif. We further show that cell signaling relays generate much steeper concentration profiles than does simple diffusion, which may facilitate neutrophil chemotaxis.
在发育、细胞凋亡和合成微生物群落等多种生物学背景下,已经证明细胞或亚细胞成分的集合可以通过利用扩散继电器来克服简单扩散的缓慢信号传递速度,其中一种可扩散信号分子的存在触发同种分子的发射参与。这种集体效应产生了快速传播的扩散波。在这里,在细胞信号转导的背景下,我们表明系统维度——细胞外介质的形状和其中细胞的分布——可以显著影响波动力学,但这些动力学对细胞激活的细节不敏感。作为一个例子,我们表明中性粒细胞群集实验表现出与所提出的信号转导模式一致的动力学特征。我们进一步表明,细胞信号转导继电器产生的浓度分布比简单扩散陡峭得多,这可能有助于中性粒细胞的趋化性。