强荷解释了细胞对联体的空间感知
Roger Oria1,2, Tina Wiegand3,4, Jorge Escribano5
1Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Technology (BIST), 08028 Barcelona, Spain.
Nature
|December 7, 2017
概括
细胞通过细胞外矩阵 (ECM) 连接物间距感知它们的环境. 这种间隔,而不是直接测量,影响细胞粘附和YAP调节,影响细胞行为.
科学领域:
- 细胞生物学
- 生物物理
- 材料科学
背景情况:
- 细胞通过整体蛋白与细胞外基质 (ECM) 相互作用以感知物理性质.
- 之前的研究表明细胞使用纳米级联体间距来调节粘附,这意味着分子统治机制.
- 整合素介导的粘附和焦点粘附形成对细胞功能至关重要,并受到物理微环境的影响.
研究的目的:
- 研究细胞如何感知ECM连接体间距和基质刚性.
- 阐明因物理信号而形成和调节焦点粘附的机制.
- 探索连接物分布和基质机制在YAP转录调节中的作用.
主要方法:
- 开发可调节的水凝基质,可控制ECM连接体密度和间距.
- 观察焦点粘附动态和细胞形态的显微镜技术.
- 使用扩展分子离合模型模拟整合素-ECM相互作用的计算建模.
- 测量细胞的引力和活动流速.
主要成果:
- 焦点粘附增长是通过增加在低刚度基板上的连接体间距促进的,但导致在高刚度基板上的粘附崩.
- 无序的连接物分布增强了粘附,但降低了崩的刚性值.
- YAP (Yes相关蛋白) 局部化 (核或细胞质) 与焦点粘附增长和崩相关.
- 分子离合模型准确地预测了基于力负荷和整合素招募的观察到的粘附动态.
结论:
- 细胞对ECM空间信息的感知是依赖于强度的整合素招募和再分配,而不是直接测量连接体间距.
- 基质刚性和连接体分布相互作用以控制焦点粘附形成,稳定性和YAP介导的转录调节.
- 这项研究为了解细胞中纳米级物理传感提供了一个框架,
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