Mechanobiological mechanism of cyclic stretch-induced cell columnarization.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-06 DOI:10.1016/j.celrep.2025.115662

Lun-Wei Lee, Gang-Hui Lee, I-Hsiu Su, Chia-Hsuan Lu, Keng-Hui Lin, Fu-Lai Wen, Ming-Jer Tang

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Abstract

In vivo, epithelial cells maintain structural integrity under dynamic mechanical perturbations. To study this, we treated various epithelial cell lines with long-term cyclic stretch (CS). Surprisingly, cells transitioned from cuboidal to columnar shape (columnarization) in MDCK cells, while others only elongated. This change correlated with actin accumulation at the top and stress fiber realignment at the bottom. Blocking mechanical stimulation via FAK inhibition or reducing vinculin partially prevented columnarization; however, disrupting tight junctions or cellular contractility substantially blocked it. The MK4 cells, derived from MDCK cells with weaker cell-cell junctions, showed less columnarization under CS, whereas overexpressing Caveolin-1 (Cav1) in MK4 cells enhanced junctions and promoted columnar formation. Atomic force microscopy studies revealed increased apical junctional stiffness in both CS-treated MDCK and Cav1-overexpressing MK4 cells. This, combined with a mathematical model, elucidated the physical characteristics and changes in cell tension post-stretch, revealing the mechanobiological foundation of epithelial cell columnarization.

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循环拉伸诱导细胞柱化的机械生物学机制。

在体内，上皮细胞在动态力学扰动下保持结构完整性。为了研究这一点，我们对多种上皮细胞系进行了长期循环拉伸（CS）处理。令人惊讶的是，MDCK细胞从立方体转变为柱状（柱化），而其他细胞只是拉长。这种变化与顶部的肌动蛋白积累和底部的应力纤维重新排列有关。通过抑制FAK抑制机械刺激或减少病毒素部分阻止柱化；然而，破坏紧密连接或细胞收缩性实质上阻止了它。MK4细胞来源于细胞间连接较弱的MDCK细胞，CS作用下，MK4细胞柱状化程度较低，而在MK4细胞中过表达Caveolin-1 （Cav1）可增强细胞间连接，促进柱状形成。原子力显微镜研究显示，cs处理的MDCK细胞和过表达cav1的MK4细胞的根尖连接刚度增加。结合数学模型，阐明了拉伸后细胞张力的物理特征和变化，揭示了上皮细胞柱化的力学生物学基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.