Epithelial Cell Chirality Revealed by Three-Dimensional Spontaneous Rotation
Epithelial Cell Chirality Revealed by Three-Dimensional Spontaneous Rotation
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DOI：
10.1073/pnas.1805932115
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发表时间：
2018-11-27
影响因子：
11.1
通讯作者：
Wan, Leo Q.
中科院分区：
文献类型：
--
作者：
Chin, Amanda S.;Worley, Kathryn E.;Wan, Leo Q.
我们对胚胎发育的左右（LR）不对称性，特别是细胞固有的手性或细胞手性的贡献的理解是有限的，这是由于在形态发生过程中混杂的系统和环境因素以及缺乏生理相关的体外3D平台。在这里，我们报告了一个有效的双层生物材料平台，用于确定单个细胞、细胞聚集体和自组织中空上皮球体的手性。这种生物工程生态位提供了一个统一的定义轴，允许细胞自发地以顺时针或逆时针方向旋转。机制研究揭示了一种肌动蛋白依赖的、细胞固有的三维手性特性，可以通过α -肌动蛋白-1介导肌动蛋白交联。我们的研究结果表明，细胞外基质的梯度是影响细胞极性和手性的重要生物物理化学线索。工程生物材料系统可以作为研究发育不对称和筛选导致出生缺陷的环境因素的有效平台。
Our understanding of the left-right (LR) asymmetry of embryonic development, in particular the contribution of intrinsic handedness of the cell or cell chirality, is limited due to the confounding systematic and environmental factors during morphogenesis and a ack of physiologically relevant in vitro 3D platforms. Here we report an efficient two-layered biomaterial platform for determining the chirality of individual cells, cell aggregates, and self-organized hollow epithelial spheroids. This bioengineered niche provides a uniform defined axis allowing for cells to rotate spontaneously with a directional bias toward either clockwise or counterclockwise directions. Mechanistic studies reveal an actin-dependent, cell-intrinsic property of 3D chirality that can be mediated by actin cross-linking via alpha-actinin-1. Our findings suggest that the gradient of extracellular matrix is an important biophysicochemical cue influencing cell polarity and chirality. Engineered biomaterial systems can serve as an effective platform for studying developmental asymmetry and screening for environmental factors causing birth defects.