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<p>Cell intercalation is the dynamic exchange of cellular neighbours responsible for tissue remodelling that occurs during embryonic morphogenesis, tissue homeostasis and wound healing. Despite extensive study in complex tissues, the minimal mechanical requirements driving intercalation remain poorly understood because of confounding tissue-level interactions. Here, we isolate the elementary unit of intercalation—a cell quadruplet—on a chip that enables quantitative force and shape measurements. Madin–Darby canine kidney epithelial cells adopt stable four-cell configurations on cross-shaped micropatterns, and spontaneously undergo T1 transitions, the type of topological rearrangement that defines intercalations. Combining live imaging with force inference and traction force microscopy, we show that intercalation emerges from two distinct mechanisms: interfacial tension dynamics and differential cell migration. We then adapt the assay to <i>Xenopus</i> mesoderm cells, revealing conserved mechanical principles across cell types. Furthermore, experimentally derived effective energy landscapes closely match theoretical vertex model predictions and suggest a dominant role for migratory forces in driving intercalation. Our minimal system provides a quantitative framework for studying intercalation mechanics in isolation and establishes a versatile platform for investigating morphogenetic processes.</p>

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A minimal in vitro assay for cell intercalation highlights the importance of interfacial tension and migratory forces

  • 期刊论文

  • 发表日期：

    2026年6月26日

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  • Artur Ruppel,
  • Vladimir Misiak,
  • Sadjad Arzash,
  • Daniel Selma-Herrador,
  • Thomas Boudou,
  • M. Lisa Manning,
  • François Fagotto,
  • Martial Balland

摘要

Cell intercalation is the dynamic exchange of cellular neighbours responsible for tissue remodelling that occurs during embryonic morphogenesis, tissue homeostasis and wound healing. Despite extensive study in complex tissues, the minimal mechanical requirements driving intercalation remain poorly understood because of confounding tissue-level interactions. Here, we isolate the elementary unit of intercalation—a cell quadruplet—on a chip that enables quantitative force and shape measurements. Madin–Darby canine kidney epithelial cells adopt stable four-cell configurations on cross-shaped micropatterns, and spontaneously undergo T1 transitions, the type of topological rearrangement that defines intercalations. Combining live imaging with force inference and traction force microscopy, we show that intercalation emerges from two distinct mechanisms: interfacial tension dynamics and differential cell migration. We then adapt the assay to Xenopus mesoderm cells, revealing conserved mechanical principles across cell types. Furthermore, experimentally derived effective energy landscapes closely match theoretical vertex model predictions and suggest a dominant role for migratory forces in driving intercalation. Our minimal system provides a quantitative framework for studying intercalation mechanics in isolation and establishes a versatile platform for investigating morphogenetic processes.