单细胞利用突出的力量在基于粘性弹性原的细胞外基质中产生迁移路径
Kolade Adebowale1,2,3, Cole Allan4, Byunghang Ha4
1Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
概括
瘤透单细胞 (免疫细胞) 通过actin聚合而通过硬,粘性矩阵迁移. 增加的矩阵刚度和更快的应激放松独立地增强了这种3D单细胞迁移,这对瘤进展至关重要.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 癌症生物学 癌症生物学
背景情况:
- 循环的单细胞透到瘤中,分化为促进瘤进展的巨细胞.
- 单细胞迁移到瘤需要穿越1型原蛋白丰富的 stromal 基质.
- 与正常组织相比,瘤 stromal 基质表现出增加的刚性和粘性弹性.
研究的目的:
- 研究矩阵刚性和粘性弹性的对三维 (3D) 单细胞迁移的影响.
- 通过限制粘弹性矩阵阐明单细胞迁移背后的机制.
主要方法:
- 利用1型原蛋白和酸盐的相互透网络来创建可调节的树皮状矩阵.
- 在3D矩阵中培养的单细胞具有独立控制的刚性和应激放松.
- 分析了单细胞形态,迁移动态,以及actin聚合和myosin收缩性的作用.
主要成果:
- 增加矩阵刚度和更快的应力放松独立增强了3D单细胞迁移.
- 单细胞表现出类似阿米形态的形态,在尾端积累了actin.
- 在前沿的行为蛋白聚合会产生突起力,使其能够通过矩阵迁移.
结论:
- 矩阵刚性和应力放松是单细胞迁移的关键调节者.
- 在3D粘弹性矩阵中的单细胞迁移依赖于actin驱动的推力.
- 了解这些机制可以为针对瘤中单细胞透的策略提供信息.
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