Miangolarra Ander Movilla, Duperray-Susini Aléria, Coppey Mathieu, Castellana Michele
Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR 168, Paris, France; Sorbonne Universités, UPMC University Paris 06, Paris, France.
Laboratoire Physico Chimie Curie, Institut Curie, PSL Research University, CNRS UMR 168, Paris, France; Sorbonne Universités, UPMC University Paris 06, Paris, France.
Biophys J. 2021 Jun 15;120(12):2394-2399. doi: 10.1016/j.bpj.2021.04.032. Epub 2021 May 4.
Protein aggregation is of particular interest because of its connection with many diseases and disorders. Many factors can alter the dynamics and result of this process, one of them being the diffusivity of the monomers and aggregates in the system. Here, we study experimentally and theoretically an aggregation process in cells, and we identify two distinct physical timescales that set the number and size of aggregates. The first timescale involves fast aggregation of small clusters freely diffusing in the cytoplasm, whereas in the second one, the aggregates are larger than the pore size of the cytoplasm and thus barely diffuse, and the aggregation process is slowed down. However, the process is not entirely halted, potentially reflecting a myriad of active but random forces that stir the aggregates. Such a slow timescale is essential to account for the experimental results of the aggregation process. These results could also have implications in other processes of spatial organization in cell biology, such as phase-separated droplets.
蛋白质聚集因其与许多疾病和功能紊乱的关联而备受关注。许多因素会改变这一过程的动力学和结果，其中之一是单体和聚集体在系统中的扩散率。在此，我们通过实验和理论研究细胞中的聚集过程，并确定了两个不同的物理时间尺度，它们决定了聚集体的数量和大小。第一个时间尺度涉及在细胞质中自由扩散的小聚集体的快速聚集，而在第二个时间尺度中，聚集体大于细胞质的孔径，因此几乎不扩散，聚集过程减慢。然而，该过程并未完全停止，这可能反映了众多搅动聚集体的活跃但随机的力。这样一个缓慢的时间尺度对于解释聚集过程的实验结果至关重要。这些结果也可能对细胞生物学中其他空间组织过程产生影响，例如相分离液滴。
