Regulation of collective cell polarity and migration using dynamically adhesive micropatterned substrates
Regulation of collective cell polarity and migration using dynamically adhesive micropatterned substrates
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DOI：
10.1016/j.actbio.2021.03.032
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发表时间：
2021-04-29
影响因子：
9.7
通讯作者：
Connelly, John T.
中科院分区：
文献类型：
--
作者：
Costa, Patricia;Blowes, Liisa M.;Connelly, John T.
细胞集体迁移是一种基本的生物过程，细胞群体以协调的方式一起移动，对组织发育和伤口修复至关重要。然而，在集体迁移细胞中协调方向性的潜在机制仍然知之甚少。在这项研究中，我们采用动态粘附微图案底物来研究粘附线索在指导上皮迁移中的作用。我们的研究结果表明，上皮细胞在响应细胞外基质（ECM）的不对称模式时集体极化，极化的程度取决于不对称的程度，并需要钙依赖性细胞-细胞粘附。当从微模式中释放出来时，上皮细胞根据预先建立的极性方向集体迁移，并且内聚迁移特别需要含有e- cadherin的粘附连接。最后，微管网络的破坏阻断了集体极化，并在功能上抑制了定向迁移。总之，这些结果表明，来自ECM的粘附信号引导集体上皮极性和迁移，这种反应依赖于粘附连接和微管。本研究采用动态粘附微图案平台来研究粘附线索在指导上皮细胞极性和定向迁移中的作用。研究结果表明，不对称组织几何形状如何影响简单上皮的集体方向性，这种反应是由粘附连接和微管网络介导的。这项工作为涉及伤口愈合的基本细胞过程提供了新的见解，并对生物材料和支架设计具有重要意义。(c) 2021 Acta Materialia Inc.Elsevier Ltd.出版。版权所有。
Collective cell migration is a fundamental biological process in which groups of cells move together in a coordinated manner, and it is essential for tissue development and wound repair. However, the underlying mechanisms that orchestrate directionality in collectively migrating cells remain poorly understood. In this study, we employed dynamically adhesive micropatterned substrates to investigate the role of adhesive cues in directing epithelial migration. Our findings demonstrate that epithelial cells collectively polarize in response to asymmetric patterns of extracellular matrix (ECM), and the degree of polarization depends on the degree of asymmetry and requires calcium-dependent cell-cell adhesion. When released from the micropatterns, epithelial cells collectively migrate according to the direction of pre-established polarity, and cohesive migration specifically requires E-cadherin-containing adherens junctions. Finally, disruption of the microtubule network blocks collective polarization and functionally inhibits directed migration. Together, these results indicate that adhesive cues from the ECM guide collective epithelial polarity and migration, and this response depends on adherens junctions and microtubules.Statement of significanceThis study employs a dynamically adhesive micropatterning platform to investigate the role of adhesive cues in directing the polarity and directional migration of epithelial cells. The findings demonstrate how asymmetric tissue geometry influences the collective directionality in simple epithelia and that this response is mediated by adherens junctions and the microtubule network. This work provides new insight into fundamental cellular processes involved in wound healing and has important implications for biomaterial and scaffold design. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.