机械诱导的同型模式域由单细胞形成
Denis Wirtz1, Wenxuan Du1, Jingyi Zhu1
1Johns Hopkins University.
Research square
|October 4, 2023
概括
人类单细胞在软矩阵上形成独特的多细胞域,由矩阵刚性和细胞信号驱动. 这种集体行为增强了单细胞的生存,并揭示了新的细胞自我组织机制.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 生物物理学的生物物理.
- 免疫学 免疫学 免疫学
背景情况:
- 矩阵刚度通过机械信号影响细胞行为和功能.
- 组织硬度对单细胞集体行为和域形成的影响尚未得到充分理解.
研究的目的:
- 为了研究生理矩阵刚性如何影响人类初级单细胞行为.
- 探索单细胞集体细胞行为和域形成背后的机制.
- 将单细胞域形成与其他免疫细胞进行比较.
主要方法:
- 使用可调节的原蛋白涂层水凝,具有生理硬性.
- 使用显微镜观察单细胞的行为,并开发了一个计算模型.
- 研究了β2整合素,可溶性抑制因子和细胞迁移的作用.
主要成果:
- 人类初级单细胞通过局部相分离在软矩阵上形成规律的,可逆的,多细胞的,多层的域.
- 域形成由β2整合素激活启动,并由全球抑制因子维持.
- 单细胞域的形成在免疫细胞中是独一无二的,通过抑制细胞化,促进细胞存活.
- 一个基于相位分离和图灵机制的计算模型准确地预测了域模式的形成.
结论:
- 单细胞可以通过利用机械感知和信号产生复杂的集体细胞阶段.
- 这种自我组织策略增强了单细胞的生存,与活性物质的行为不同.
- 这些发现揭示了先天性免疫细胞中细胞生存和集体行为的新机制.
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