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PI3K inhibition reverses migratory direction of single cells but not cell groups in electric field
bioRxiv - Biophysics Pub Date : 2020-08-06 , DOI: 10.1101/2020.08.05.238170
Y Sun , H Yue , C Copos , K Zhu , Y Zhang , Y Sun , X Gao , B Reid , F Lin , M Zhao , A Mogilner

Motile cells migrate directionally in the electric field in a process known as galvanotaxis. Galvanotaxis is important in wound healing, development, cell division, and nerve growth. Different cell types migrate in opposite directions in electric fields, to either cathode, or anode, and the same cell can switch the directionality depending on chemical conditions. We previously reported that individual fish keratocyte cells sense electric fields and migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Many physiological processes rely on collective, not individual, cell migration, so here we report on directional migration of cohesive cell groups in electric fields. Uninhibited cell groups of any size move to the cathode, with speed decreasing and directionality increasing with the group size. Surprisingly, large groups of PI3K-inhibited cells move to the cathode, in the direction opposite to that of individual cells, which move to the anode, while such small groups are not persistently directional. In the large groups, cells' velocities are distributed unevenly: the fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. Our results are most consistent with the hypothesis, supported by the computational model, that cells inside and at the edge of the groups interpret directional signals differently. Namely, cells in the group interior are directed to the cathode independently of their chemical state. Meanwhile, edge cells behave like the individual cells: they are directed to the cathode/anode in uninhibited/PI3K-inhibited groups, respectively. As a result, all cells drive uninhibited groups to the cathode, but a mechanical tug-of-war between the inner and edge cells directs large PI3K-inhibited groups with cell majority in the interior to the cathode, while rendering small groups non-directional.

中文翻译:

PI3K抑制逆转单个细胞的迁移方向,但不能逆转电场中的细胞组

运动细胞在电场中定向迁移,这种过程称为电刺激。触痛在伤口愈合,发育,细胞分裂和神经生长中很重要。不同的电池类型在电场中向相反的方向迁移到阴极或阳极,并且同一电池可以根据化学条件切换方向。我们之前曾报道过,单个鱼角质形成细胞会感应电场并迁移到阴极,而PI3K的抑制则会使单个细胞反转到阳极。许多生理过程依赖于集体而不是个体的细胞迁移,因此在这里我们报告电场中粘性细胞群的定向迁移。任意大小的不受抑制的电池组都会移动到阴极,随着组大小的增加,速度会降低,方向性会增加。出奇,大群受PI3K抑制的细胞以与单个细胞相反的方向移动到阴极,而单个细胞则移动到阳极,而这些小组却不是永久定向的。在大的组中,细胞的速度分布不均匀:最快的细胞在未抑制组的前面,但在PI3K抑制组的中间和后面。我们的结果与计算模型所支持的假说最一致,该假说认为,小组内部和小组边缘的细胞对方向信号的解释不同。即,组内部的电池独立于其化学状态而被引导至阴极。同时,边缘细胞的行为类似于单个细胞:它们分别以未抑制/ PI3K抑制的组被导向阴极/阳极。结果是,
更新日期:2020-08-06
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