Ciliary behaviour and mechano-transduction in the embryonic node: Computational testing of hypotheses

Ciliary behaviour and mechano-transduction in the embryonic node: Computational testing of hypotheses
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DOI:
10.1016/j.medengphy.2010.10.020
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发表时间:
2011-09-01
影响因子:
2.2
通讯作者:
Ventikos, Yiannis
Ventikos, Yiannis
中科院分区:
工程技术3区
文献类型:
--
作者:
Chen, Duanduan;Norris, Dominic;Ventikos, Yiannis

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哺乳动物胚胎中的左右对称性破缺被认为发生在一个短暂的胚胎结构中,即节点:该结构内纤毛的旋转运动产生了液体的反向流动,这是观察到的第一个不对称事件。一种假说,通常被称为“双纤毛”假说,提出节点包含两种初级纤毛:运动纤毛,由马达蛋白驱动,顺时针旋转产生反流和被动纤毛,作为机械传感器,对出现的流量进行机械反应。尽管有几项研究试图阐明所涉及的过程,但最初对称性破缺的确切机制仍不清楚。在本文中,我们提出了两个计算模型(一)模拟的单向流动引起的主动纤毛运动,以及他们的推进被动纤毛和(ii)调查的蛋白质活性,产生主动纤毛旋转样运动。所提出的模型结合了计算流体动力学、变形网格计算技术和流固耦合分析的方法。通过求解三维非定常输运方程,与适当的边界条件,我们证实,主动纤毛的旋转运动是能够诱导的单向流动,被动纤毛被推向左侧的纤毛长度的41.7%的尖端上的可见变形,支持双纤毛假设的可验证性。此外,通过应用有限元分析和网格变形技术,我们调查纤毛运动所触发的蛋白马达的激活,并提出了一种可能的动力蛋白激活模式,能够产生顺时针旋转的胚胎纤毛。(C)20101PEM。出版社:Elsevier Lid All rights reserved.
Left-right symmetry breaking in the mammalian embryo is believed to occur in a transient embryonic structure, the node: rotational motion of cilia within this structure creates a leftward flow of liquid that is the first asymmetric event observed. A hypothesis, often referred to as the "two-cilia" hypothesis, proposes that the node contains two kinds of primary cilia: motile cilia, driven by motor proteins, that rotate clockwise generating the leftward flow and passive cilia that act as mechano-sensors, reacting mechanically to the emerging flow. The exact mechanism that underlies the initial breaking of symmetry remains unclear, in spite of several studies that have attempted to elucidate the processes involved. In this paper, we present two computational models to (i) simulate the unidirectional flow induced by the active ciliary motion as well as their propulsion on the passive cilia and to (ii) investigate the protein activity that produces the active ciliary rotation-like movement. The models presented incorporate methodologies from computational fluid dynamics, deformable mesh computational techniques and fluid-structure interaction analysis. By solving the three-dimensional unsteady transport equations, with suitable boundary conditions, we confirm that the whirling motion of active cilia is capable of inducing the unidirectional flow and that the passive cilia are pushed by this flow towards the left with a visible deformation of 41.7% of the ciliary length on the tip, supporting the plausibility of the two-cilia hypothesis. Further, by applying finite element analysis and grid deformation techniques, we investigate the ciliary motion triggered by the activation of protein motors and propose a possible dynein activation pattern that is able to produce the clockwise rotation of embryonic cilia. (C) 20101PEM. Published by Elsevier Lid. All rights reserved.