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<p>Cells decode mechanical cues to direct fate decisions through nuclear remodeling, yet nuclear adaptors to mechanical signals remain elusive. Here, we show that soft matrix suppresses myoblast differentiation and induces nuclear abnormality within 30 min, accompanied by a greater than 60% reduction in lamin B1 proteins levels. Mechanistically, midnolin interacts with lamin B1 and mediates ubiquitination-independent degradation of lamin B1 on soft matrix, through the Catch domain of midnolin engaging a β-strand within lamin B1’s Ig-like domain. Functionally, moderate lamin B1 expression is essential for myoblast differentiation initiation, as its depletion either by siRNA or CRISPR knockout abolishes myogenic capacity. Our findings reveal that the midnolin-proteasome axis directly converts mechanical inputs into lineage commitment by triggering lamin B1 degradation, defining a novel nuclear mechano-adaptation pathway.</p>

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Matrix stiffness induces midnolin-dependent lamin B1 degradation to control myoblast differentiation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月31日

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  • Liping Guo,
  • Yanjing Zhao,
  • Zhe Zhang,
  • Chang Sun,
  • Yafan Xie,
  • Qin Dai,
  • Yan Yan,
  • Yaoqi Zhou,
  • Yang Zhang,
  • Quhuan Li,
  • Juhui Qiu,
  • Qin Peng

摘要

Cells decode mechanical cues to direct fate decisions through nuclear remodeling, yet nuclear adaptors to mechanical signals remain elusive. Here, we show that soft matrix suppresses myoblast differentiation and induces nuclear abnormality within 30 min, accompanied by a greater than 60% reduction in lamin B1 proteins levels. Mechanistically, midnolin interacts with lamin B1 and mediates ubiquitination-independent degradation of lamin B1 on soft matrix, through the Catch domain of midnolin engaging a β-strand within lamin B1’s Ig-like domain. Functionally, moderate lamin B1 expression is essential for myoblast differentiation initiation, as its depletion either by siRNA or CRISPR knockout abolishes myogenic capacity. Our findings reveal that the midnolin-proteasome axis directly converts mechanical inputs into lineage commitment by triggering lamin B1 degradation, defining a novel nuclear mechano-adaptation pathway.