维门通过增加的矩阵重塑和球状流动性,通过原网络促进集体细胞迁移
Minh Tri Ho Thanh1,2, Arun Poudel2,3, Shabeeb Ameen1,2
1Physics Department, Syracuse University; Syracuse, New York, USA.
bioRxiv : the preprint server for biology
|July 1, 2024
概括
维门是一种关键的中间丝蛋白,对于3D环境中的集体细胞迁移至关重要. 它的缺失会损害细胞运动和细胞外矩阵重塑,突出显示它在疾病进展中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 生物化学 生物化学
背景情况:
- 介质丝蛋白维门丁 (vimentin) 与细胞迁移和入侵增加的疾病有关.
- 维门在体内集体细胞迁移中的确切作用,特别是在细胞外基质 (ECM) 中,仍然不完全理解.
- 虽然维门丁影响细胞粘附和力生成,但它也可以阻碍通过密集矩阵的迁移.
研究的目的:
- 阐明维门丁在三维 (3D) 细胞外矩阵内的集体细胞迁移中的功能.
- 为了研究维门如何影响球状膨胀,矩阵重塑和3D原环境中的力生成.
主要方法:
- 产生维门野生型和维门零型小鼠胚胎纤维细胞 (mEF) 球体.
- 在3D原基质中嵌入球体,用于集体细胞迁移测试.
- 使用引力显微镜和3D顶点模型模拟.
主要成果:
- 维门的损失显著减少了球状集体扩张和原网络重塑.
- 与野生类型球体相比,维丁无球体表现出减少的收缩力.
- 丝状维门,不仅仅是它的存在,对于促进3D集体细胞迁移至关重要,这是用维门单位长度丝 (ULF) 进行的研究证明的.
- 维门丁介导的迁移依赖于矩阵金属蛋白酶 (MMP) 活性来降解原蛋白.
- 野生型球体表现出更像流体的行为,促进矩阵操纵和迁移.
结论:
- 维门在增强3D矩阵环境中的迁徙持久性方面发挥着至关重要的作用.
- 维门通过涉及MMP运输和促进组织流动性的机制促进了集体细胞迁移.
- 这些发现强调了维门在与疾病发病相关的细胞过程中的重要性.
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