破坏核-细胞骨连接会损害上皮细胞的机械感知和集体迁移
1Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, Missouri, United States.
Biophysical journal
|March 15, 2026
概括
破坏核骨和细胞骨 (LINC) 复杂的连接器会损害在不同硬度的表面上上皮质细胞的迁移. 受到LINC干扰的细胞表现出减少的机械感知和改变的细胞力学,影响集体细胞行为.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 机械生物学 机械生物学
背景情况:
- 核骨和细胞骨的连接器 (LINC) 综合体将细胞核与细胞骨连接起来,影响细胞功能.
- 已知单细胞迁移中的LINC复杂作用,但其对集体上皮细胞迁移的影响尚不清楚.
研究的目的:
- 调查LINC复合体在集体上皮质细胞迁移在具有不同硬度的基板上的作用.
- 了解LINC复杂干扰如何影响细胞力学和机械感知.
主要方法:
- 使用可诱导的主导-负 SUN1 构造 (SUN1L) 来破坏 MCF10A 乳腺上皮细胞中的 LINC 功能.
- 在不同硬度 (0.1,5,50 kPa) 的原涂层聚烯胺水凝上培养的细胞.
- 分析了细胞迁移速度,度灵敏度,细胞/组织力学,粘附性和actomyosin收缩性.
主要成果:
- 经过LINC破坏的细胞在所有测试的度中表现出较慢的迁移速度.
- SUN1L细胞显示度敏感性降低,表明机械感知功能受损.
- 这种LINC的破坏导致了更小,更软的细胞,更密集的上皮层,更强的细胞矩阵粘附,以及减少了actomyosin的收缩性.
结论:
- 通过LINC破坏的核细胞骨脱会诱导多个尺度的物理变化,从而损害机械敏感的集体细胞迁移.
- 林克复合体的功能障碍可能通过改变集体细胞行为,影响疾病进展,包括癌症和层状病变.
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