Division of Cell Physics, Department of Applied Physics, Royal Institute of Technology, Stockholm, Sweden.
Am J Physiol Renal Physiol. 2010 May;298(5):F1096-102. doi: 10.1152/ajprenal.00657.2009. Epub 2010 Jan 20.
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.
纤毛是一种普遍存在于大多数哺乳动物细胞上的细胞器。该细胞器的功能障碍与各种病理紊乱有关，其中许多紊乱会导致肝脏、胰腺和肾脏的囊性疾病。在肾上皮细胞中，观察到纤毛对流体流动产生细胞内钙，并且参与该钙信号的蛋白质的破坏导致常染色体显性多囊肾病，这意味着钙信号和囊肿形成之间存在直接联系。也已经表明，在开始流动和开始钙信号之间存在明显的滞后。本研究专注于纤毛弯曲的力学及其导致的钙信号。对不同类型施加的流刺激下实时纤毛运动的可视化显示，与钙增加的起始相比，弯曲非常迅速。对纤毛和周围膜进行数学建模，以推断弯曲和膜应力之间的关系。结果表明，应力的建立存在延迟，与钙信号的延迟相似。因此，我们的结果表明，纤毛弯曲时钙反应的延迟是由细胞膜的力学特性引起的。
