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Mapping Local and Global Liquid Phase Behavior in Living Cells Using Photo-Oligomerizable Seeds.
Cell ( IF 45.5 ) Pub Date : 2018-Nov-29 , DOI: 10.1016/j.cell.2018.10.048 Dan Bracha 1 , Mackenzie T Walls 1 , Ming-Tzo Wei 1 , Lian Zhu 1 , Martin Kurian 1 , José L Avalos 2 , Jared E Toettcher 3 , Clifford P Brangwynne 4
Cell ( IF 45.5 ) Pub Date : 2018-Nov-29 , DOI: 10.1016/j.cell.2018.10.048 Dan Bracha 1 , Mackenzie T Walls 1 , Ming-Tzo Wei 1 , Lian Zhu 1 , Martin Kurian 1 , José L Avalos 2 , Jared E Toettcher 3 , Clifford P Brangwynne 4
Affiliation
Liquid-liquid phase separation plays a key role in the assembly of diverse intracellular structures. However, the biophysical principles by which phase separation can be precisely localized within subregions of the cell are still largely unclear, particularly for low-abundance proteins. Here, we introduce an oligomerizing biomimetic system, "Corelets," and utilize its rapid and quantitative light-controlled tunability to map full intracellular phase diagrams, which dictate the concentrations at which phase separation occurs and the transition mechanism, in a protein sequence dependent manner. Surprisingly, both experiments and simulations show that while intracellular concentrations may be insufficient for global phase separation, sequestering protein ligands to slowly diffusing nucleation centers can move the cell into a different region of the phase diagram, resulting in localized phase separation. This diffusive capture mechanism liberates the cell from the constraints of global protein abundance and is likely exploited to pattern condensates associated with diverse biological processes. VIDEO ABSTRACT.
中文翻译:
使用光可聚合种子在活细胞中绘制局部和全局液相行为图。
液-液相分离在多种细胞内结构的组装中起关键作用。但是,对于相分离可精确定位在细胞亚区域内的生物物理原理仍然不清楚,特别是对于低丰度蛋白。在这里,我们介绍了一种低聚仿生系统“ Corelets”,并利用其快速和定量的光控可调性绘制完整的细胞内相图,该图以蛋白质序列依赖性的方式指示了发生相分离的浓度和过渡机制。 。令人惊讶的是,实验和模拟均表明,虽然细胞内浓度可能不足以进行整体相分离,螯合蛋白质配体至缓慢扩散的成核中心可使细胞进入相图的不同区域,从而导致局部相分离。这种扩散性捕获机制将细胞从全局蛋白质丰度的限制中解放出来,并且很可能被用来对与多种生物过程相关的冷凝物进行模式化。视频摘要。
更新日期:2018-11-30
中文翻译:
使用光可聚合种子在活细胞中绘制局部和全局液相行为图。
液-液相分离在多种细胞内结构的组装中起关键作用。但是,对于相分离可精确定位在细胞亚区域内的生物物理原理仍然不清楚,特别是对于低丰度蛋白。在这里,我们介绍了一种低聚仿生系统“ Corelets”,并利用其快速和定量的光控可调性绘制完整的细胞内相图,该图以蛋白质序列依赖性的方式指示了发生相分离的浓度和过渡机制。 。令人惊讶的是,实验和模拟均表明,虽然细胞内浓度可能不足以进行整体相分离,螯合蛋白质配体至缓慢扩散的成核中心可使细胞进入相图的不同区域,从而导致局部相分离。这种扩散性捕获机制将细胞从全局蛋白质丰度的限制中解放出来,并且很可能被用来对与多种生物过程相关的冷凝物进行模式化。视频摘要。