Quantifying cellular and subcellular stretches in embryonic lung epithelia under peristalsis: where to look for mechanosensing
Quantifying cellular and subcellular stretches in embryonic lung epithelia under peristalsis: where to look for mechanosensing
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DOI：
10.1098/rsfs.2016.0031
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发表时间：
2016-10-06
期刊：
影响因子：
4.4
通讯作者：
Lubkin, Sharon R.
中科院分区：
文献类型：
--
作者：
Bokka, Kishore K.;Jesudason, Edwin C.;Lubkin, Sharon R.
肺内的蠕动从平滑肌（SM）形成时就开始了，一直持续到出生。由于产前肺充满液体，SM作用可以通过管腔压力使远离紧邻组织的组织变形。胚胎组织的拉伸已被证明具有强有力的形态发生效应。我们假设这些效应在肺形态发生中起作用。为了在定量框架中完善这一广泛的假设，我们从几何学上分析了上皮组织中的细胞形状，以及完全阻塞气道的蠕动波引起的单个细胞变形。典型的畸变可能非常大，在茎部和尖端区域具有相反的取向。顶端扭曲总是大于基底扭曲。我们给出了阻塞气道长度和远端尖端组织拉伸之间关系的定量估计。我们完善我们的分析细胞应力和应变从peptisis与一个简单的力学模型的变形细胞内的上皮细胞，占基本的亚细胞几何形状和材料特性。该模型确定了可能的应力集中在细胞核附近和顶端细胞-细胞连接处。令人惊讶的大应变的气道纤维化可能有助于重新排列细胞和刺激其他机械敏感的过程，通过反复对齐细胞骨架成分和/或打破和重组横向细胞-细胞粘附。相邻细胞的细胞核之间的应力集中可以用作引导细胞核随着上皮成熟而对齐的机械控制机制。
Peristalsis begins in the lung as soon as the smooth muscle (SM) forms, and persists until birth. As the prenatal lung is filled with liquid, SM action can, through lumen pressure, deform tissues far from the immediately adjacent tissues. Stretching of embryonic tissues has been shown to have potent morphogenetic effects. We hypothesize that these effects are at work in lung morphogenesis. In order to refine that broad hypothesis in a quantitative framework, we geometrically analyse cell shapes in an epithelial tissue, and individual cell deformations resulting from peristaltic waves that completely occlude the airway. Typical distortions can be very large, with opposite orientations in the stalk and tip regions. Apical distortions are always greater than basal distortions. We give a quantitative estimate of the relationship between length of occluded airway and the resulting tissue stretch in the distal tip. We refine our analysis of cell stresses and strains from peristalsis with a simple mechanical model of deformation of cells within an epithelium, which accounts for basic subcellular geometry and material properties. The model identifies likely stress concentrations near the nucleus and at the apical cell-cell junction. The surprisingly large strains of airway peristalsis may serve to rearrange cells and stimulate other mechanosensitive processes by repeatedly aligning cytoskeletal components and/or breaking and reforming lateral cell-cell adhesions. Stress concentrations between nuclei of adjacent cells may serve as a mechanical control mechanism guiding the alignment of nuclei as an epithelium matures.