Narciso Cody, Wu Qinfeng, Brodskiy Pavel, Garston George, Baker Ruth, Fletcher Alexander, Zartman Jeremiah
Department of Chemical and Biomolecular Engineering, University of Notre Dame, 182 Fitzpatrick Hall, Notre Dame, IN 46556, USA.
Phys Biol. 2015 Sep 2;12(5):056005. doi: 10.1088/1478-3975/12/5/056005.
Differential mechanical force distributions are increasingly recognized to provide important feedback into the control of an organ's final size and shape. As a second messenger that integrates and relays mechanical information to the cell, calcium ions (Ca(2+)) are a prime candidate for providing important information on both the overall mechanical state of the tissue and resulting behavior at the individual-cell level during development. Still, how the spatiotemporal properties of Ca(2+) transients reflect the underlying mechanical characteristics of tissues is still poorly understood. Here we use an established model system of an epithelial tissue, the Drosophila wing imaginal disc, to investigate how tissue properties impact the propagation of Ca(2+) transients induced by laser ablation. The resulting intercellular Ca(2+) flash is found to be mediated by inositol 1,4,5-trisphosphate and depends on gap junction communication. Further, we find that intercellular Ca(2+) transients show spatially non-uniform characteristics across the proximal-distal axis of the larval wing imaginal disc, which exhibit a gradient in cell size and anisotropy. A computational model of Ca(2+) transients is employed to identify the principle factors explaining the spatiotemporal patterning dynamics of intercellular Ca(2+) flashes. The relative Ca(2+) flash anisotropy is principally explained by local cell shape anisotropy. Further, Ca(2+) velocities are relatively uniform throughout the wing disc, irrespective of cell size or anisotropy. This can be explained by the opposing effects of cell diameter and cell elongation on intercellular Ca(2+) propagation. Thus, intercellular Ca(2+) transients follow lines of mechanical tension at velocities that are largely independent of tissue heterogeneity and reflect the mechanical state of the underlying tissue.
不同的机械力分布越来越被认为能为器官最终大小和形状的控制提供重要反馈。作为一种整合并将机械信息传递给细胞的第二信使，钙离子（Ca(2+)）是在发育过程中提供有关组织整体机械状态和单个细胞水平上的行为的重要信息的主要候选者。然而，Ca(2+)瞬变的时空特性如何反映组织潜在的机械特性仍知之甚少。在这里，我们使用上皮组织的一个既定模型系统——果蝇翅成虫盘，来研究组织特性如何影响激光消融诱导的Ca(2+)瞬变的传播。结果发现，细胞间的Ca(2+)闪光是由肌醇1,4,5-三磷酸介导的，并且依赖于间隙连接通讯。此外，我们发现细胞间Ca(2+)瞬变在幼虫翅成虫盘的近端-远端轴上呈现出空间不均匀的特征，该轴在细胞大小和各向异性上呈现出梯度。我们采用Ca(2+)瞬变的计算模型来确定解释细胞间Ca(2+)闪光时空模式动态的主要因素。相对Ca(2+)闪光各向异性主要由局部细胞形状各向异性解释。此外，整个翅盘中Ca(2+)速度相对均匀，与细胞大小或各向异性无关。这可以通过细胞直径和细胞伸长对细胞间Ca(2+)传播的相反作用来解释。因此，细胞间Ca(2+)瞬变沿着机械张力线传播，速度在很大程度上独立于组织异质性，并反映了下层组织的机械状态。
