Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation.
Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation.
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DOI：
10.1016/j.devcel.2018.03.011
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发表时间：
2018-04-09
影响因子：
11.8
通讯作者：
Ewald AJ
中科院分区：
文献类型：
--
作者：
Neumann NM;Perrone MC;Veldhuis JH;Huebner RJ;Zhan H;Devreotes PN;Brodland GW;Ewald AJ
我们试图了解细胞如何共同拉长上皮管。我们首先使用3D培养和生物传感器成像来证明上皮细胞在组织内迁移过程中将RAS活性、PIP3和F-肌动蛋白丰富到它们的前沿。与单细胞相比，PIP3的增加恰好与F-肌动蛋白的动态变化相吻合，并且在抑制F-肌动蛋白的动态变化的情况下仍然可以增加，这揭示了一种保守的迁移逻辑。我们发现，迁移细胞可以插入到基底组织表面，并有助于管子的延长。然后，我们使用力推理分析将分子活动与亚细胞力学联系起来。迁移和瞬时插层需要特定的和相似的前后界面张力比率。永久性夹层的区别在于它们通过时变的张力动力学在边界上被捕获。最后，我们将实验数据和计算数据结合起来，建立了管材拉伸的有限元模型。我们的模型表明，插层、界面张力动力学和较高的基础应力共同足以实现乳腺形态发生。Neumann等人。证明哺乳动物组织内的上皮细胞和平面底物上的单个细胞之间的空间不对称性和迁移的分子逻辑是保守的。力推断技术和有限元建模进一步定义了一组机械性能和细胞行为，包括径向插层，延长了管子。
We sought to understand how cells collectively elongate epithelial tubes. We first used 3D culture and biosensor imaging to demonstrate that epithelial cells enrich Ras activity, PIP3, and F-actin to their leading edges during migration within tissues. PIP3 enrichment coincided with, and could enrich despite inhibition of, F-actin dynamics, revealing a conserved migratory logic compared to single cells. We discovered that migratory cells can intercalate into the basal tissue surface and contribute to tube elongation. We then connected molecular activities to subcellular mechanics using force inference analysis. Migration and transient intercalation required specific and similar anterior-posterior ratios of interfacial tension. Permanent intercalations were distinguished by their capture at the boundary through time-varying tension dynamics. Finally, we integrated our experimental and computational data to generate a finite element model of tube elongation. Our model revealed that intercalation, interfacial tension dynamics, and high basal stress are together sufficient for mammary morphogenesis. Neumann et al. demonstrate that the spatial asymmetries and molecular logic of migration are conserved between epithelial cells within mammalian tissues and single cells on flat substrates. Force inference techniques and finite element modeling further define a set of mechanical properties and cell behaviors, including radial intercalation, that elongate tubes.
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影响因子：
4.6
作者：
Huebner, Robert J.;Neumann, Neil M.;Ewald, Andrew J.
通讯作者：
Ewald, Andrew J.
在哺乳动物组织形态发生中，细胞嵌入产生的力牵引表皮片。
影响因子：
11.8
作者：
Heller, Evan;Kumar, K. Vijay;Grill, Stephan W.;Fuchs, Elaine
通讯作者：
Fuchs, Elaine
影响因子：
8
作者：
Artemenko, Yulia;Lampert, Thomas J.;Devreotes, Peter N.
通讯作者：
Devreotes, Peter N.
影响因子：
11.8
作者：
Mailleux, Arnaud A.;Overholtzer, Michael;Brugge, Joan S.
通讯作者：
Brugge, Joan S.
影响因子：
7.2
作者：
Devreotes, Peter;Horwitz, Alan Rick
通讯作者：
Horwitz, Alan Rick