Force fluctuations and polymerization dynamics of intracellular microtubules

Force fluctuations and polymerization dynamics of intracellular microtubules
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DOI:
10.1073/pnas.0703094104
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发表时间:
2007-10-09
影响因子:
11.1
通讯作者:
Weitz, David A.
Weitz, David A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Brangwynne, Clifford P.;MacKintosh, F. C.;Weitz, David A.

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微管是一种高度动态的生物聚合物细丝,参与多种生物过程,包括细胞分裂、迁移和细胞内运输。微管非常坚硬,形成了一个坚硬的结构支架,可以抵抗变形。然而,尽管它们坚硬,但在细胞内部,它们通常在所有长度的尺度上都表现出显著的弯曲。在这里,我们使用傅立叶分析方法来研究这些弯曲的起源,以量化它们的长度和时间相关性。我们发现,在培养的动物细胞中,弯曲被周围的弹性细胞骨架抑制,即使是很大的细胞内力也只会在较短的尺度上引起显著的弯曲波动。然而,这些横向弯曲波动也自然引起微管尖端取向的波动。在生长过程中,这些尖端的波动导致微管弯曲,这些弯曲被周围的弹性网络冻结。这导致了微管的持续随机行走,其小的表观持续长度约为30微米,约为仅由热波动引起的微管持续长度的100倍。因此,大的非热力控制着微管的生长,并可以解释在活细胞的微管细胞骨架中观察到的高度弯曲的形状。
Microtubules are highly dynamic biopolymer filaments involved in a wide variety of biological processes including cell division, migration, and intracellular transport. Microtubules are very rigid and form a stiff structural scaffold that resists deformation. However, despite their rigidity, inside of cells they typically exhibit significant bends on all length scales. Here, we investigate the origin of these bends using a Fourier analysis approach to quantify their length and time dependence. We show that, in cultured animal cells, bending is suppressed by the surrounding elastic cytoskeleton, and even large intracellular forces only cause significant bending fluctuations on short length scales. However, these lateral bending fluctuations also naturally cause fluctuations in the orientation of the microtubule tip. During growth, these tip fluctuations lead to microtubule bends that are frozen-in by the surrounding elastic network. This results in a persistent random walk of the microtubule, with a small apparent persistence length of approximate to 30 mu m, approximate to 100 times smaller than that resulting from thermal fluctuations alone. Thus, large nonthermal forces govern the growth of microtubules and can explain the highly curved shapes observed in the microtubule cytoskeleton of living cells.