Mechanical properties of primary cilia regulate the response to fluid flow
Mechanical properties of primary cilia regulate the response to fluid flow
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DOI：
10.1152/ajprenal.00657.2009
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发表时间：
2010-05-01
影响因子：
4.2
通讯作者：
Brismar, Hjalmar
中科院分区：
文献类型：
--
作者：
Rydholm, Susanna;Zwartz, Gordon;Brismar, Hjalmar
[10]李国雄，李国雄.初级纤毛的机械特性调节对流体流动的反应。美国肾脏生理学杂志298：F1096-F1102，2010年。首次发表于2010年1月20日; doi：10.1152/ajprenal.00657.2009。初级纤毛是存在于大多数哺乳动物细胞中的普遍存在的细胞器。细胞器的功能障碍与各种病理性疾病有关，其中许多导致肝脏、胰腺和肾脏中的囊性疾病。已经观察到肾上皮细胞中的初级纤毛响应于流体流动而产生细胞内钙，并且参与这种钙信号传导的蛋白质的破坏导致常染色体显性多囊肾病，这意味着钙信号传导和囊肿形成之间的直接联系。还表明，在流动的开始和钙信号的起始之间存在显著的滞后。本研究的重点是纤毛弯曲的力学和由此产生的钙信号。实时纤毛运动响应于不同类型的应用流的可视化表明，弯曲是快速的钙增加的开始相比。建立了纤毛及周围膜的数学模型，推导了纤毛弯曲与膜应力的关系。结果显示，应力积累的延迟与钙信号的延迟相似。因此，我们的研究结果表明，纤毛弯曲后钙反应的延迟是由细胞膜的机械性能。
Rydholm S, Zwartz G, Kowalewski JM, Kamali-Zare P, Frisk T, Brismar H. Mechanical properties of primary cilia regulate the response to fluid flow. Am J Physiol Renal Physiol 298: F1096-F1102, 2010. First published January 20, 2010; doi:10.1152/ajprenal.00657.2009.-The primary cilium is a ubiquitous organelle present on most mammalian cells. Malfunction of the organelle has been associated with various pathological disorders, many of which lead to cystic disorders in liver, pancreas, and kidney. Primary cilia have in kidney epithelial cells been observed to generate intracellular calcium in response to fluid flow, and disruption of proteins involved in this calcium signaling lead to autosomal dominant polycystic kidney disease, implying a direct connection between calcium signaling and cyst formation. It has also been shown that there is a significant lag between the onset of flow and initiation of the calcium signal. The present study focuses on the mechanics of cilium bending and the resulting calcium signal. Visualization of real-time cilium movements in response to different types of applied flow showed that the bending is fast compared with the initiation of calcium increase. Mathematical modeling of cilium and surrounding membrane was performed to deduce the relation between bending and membrane stress. The results showed a delay in stress buildup that was similar to the delay in calcium signal. Our results thus indicate that the delay in calcium response upon cilia bending is caused by mechanical properties of the cell membrane.