细胞介导的基质变形和细胞-细胞粘附决定了表皮细胞集体细胞迁移表型
Corinne E Leonard1, Jessanne Y Lichtenberg1, Hazel R Sterling1
1Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia 23284, USA.
APL bioengineering
|December 22, 2025
概括
表皮细胞使用旋转和侵入性迁移来形成组织. 在造过程中,P-cadherin (CDH3) 对于过渡到侵入性迁移至关重要,这是一个受细胞矩阵相互作用影响的过程.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学是发展生物学.
- 生物物理学的生物物理.
背景情况:
- 组织发育依赖于集体细胞迁移表型,如旋转 (状结构) 和侵入性 (管状结构).
- 控制这些独特的细胞迁移模式在上皮层形态发生过程中的机制,如管体发生,仍然不太了解.
- P-cadherin (CDH3) 和细胞矩阵相互作用与细胞迁移有关,但它们在表型切换中的具体作用尚不清楚.
研究的目的:
- 为了研究P-cadherin (CDH3) 和机械细胞矩阵相互作用如何影响旋转与侵入性集体细胞迁移表型在管体发生过程中.
- 阐明CDH3在迁移表型之间的过渡中的作用及其对矩阵变形的影响.
- 确定RhoA激活是否可以在CDH3贫乏细胞中拯救侵入性迁移表型.
主要方法:
- 使用定制的3D微流体检测,用于造过程中野生类型 (WT) 和CDH3-贫乏 (CDH3-/-) 表皮囊的活细胞成像.
- 同时测量了矩阵变形率和观察到的细胞矩阵相互作用,包括焦点粘附.
- 操纵RhoA信号,以评估其对CDH3缺乏细胞的影响.
主要成果:
- WT上皮囊最初表现出旋转型表型,并过渡到导管生成的侵入性表型.
- 侵袭性集体迁移 (ICM) 现型与旋转性现型相比,与更高的矩阵变形率相关.
- CDH3对于过渡到ICM表型至关重要,其耗尽会降低矩阵变形率.
- CDH3的损失会损害ICM,但可以通过RhoA激活来挽救,从而增加矩阵变形和素招募.
结论:
- 在造过程中,CDH3在使上皮囊从旋转转向侵入性迁移表型的转换中发挥着关键作用.
- 机械细胞矩阵相互作用,特别是矩阵变形率,是集体细胞迁移表型的关键调节者.
- 罗亚信号传递是一种下游效应因子,可以恢复CDH3缺乏细胞的侵入性迁移,突出其在调节细胞矩阵动态和组织形态发生方面的重要性.
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