基于N-Cadherin的粘附和Rac1的活动调节了actin皮质中的张力极化
Seyedsajad Moazzeni1,2, Kelly Kyker-Snowman2, Rick I Cohen2
1Department of Mechanical & Aerospace Engineering, Rutgers, The State University of New Jersey, 98 Brett Rd, Piscataway, NJ, 08854, USA.
Scientific reports
|February 5, 2025
概括
通过调节外部和内部接口张力,N-cadherin驱动细胞中的张力极化. Rac1作为一个开关,控制组织重塑和癌症进展的actin-myosin收缩性.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 发育生物学是发展生物学.
背景情况:
- 张力-粘附相互作用对多细胞组织至关重要,影响组织表面张力,细胞分类和形态发生.
- 卡德林参与了这个过程,但它们的确切角色和定量贡献仍然不清楚.
- 了解这些机制对于从发育生物学到癌症研究等领域至关重要.
研究的目的:
- 阐明N-cadherin在actin皮质网络中的张力极化中的作用.
- 量化N-cadherin密度和细胞-细胞接口对张力差异的影响.
- 为了识别分子介导体,如Rac1,将cadherins与actin-myosin收缩性联系起来.
主要方法:
- 通过生物物理技术测量细胞界面的力量,研究了张力极化.
- 操纵N-cadherin表面密度和细胞群大小,以评估它们对张力的影响.
- 利用Rac1的药理性抑制来确定其在德林-动因收缩性途径中的作用.
主要成果:
- N-cadherin极大地推动了张力极化,在细胞介质接口上增加了张力,在细胞-细胞接口上降低了张力.
- 张力调节的大小直接取决于N-cadherin表面密度.
- 张力极化强度与多细胞集群中细胞-细胞接口的数量相关.
- Rac1的激活对于通过myosin II进行卡德林介导的皮质重塑和收缩是必不可少的.
- 抑制Rac1会破坏细胞群和球体中的张力极化和连贯性.
结论:
- N-cadherin 作为紧张两极分化的关键调节剂,其作用量取决于表面密度和细胞环境.
- Rac1-myosin II 途径介导着卡德林与行为皮层重塑之间的联系,这对组织力学至关重要.
- 这些发现为组织表面张力产生提供了统一的视角,并为癌症治疗提供了潜在的治疗点.
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