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<p>Tissue spheroids fuse to form larger tissue structures, a process controlled by their living material properties. However, how these properties emerge from the active behavior of individual cells is not well understood. Here, we studied fusion dynamics of spheroids from human periosteum-derived cells. Using confocal microscopy, we measured spheroid granularity and, with two-photon microscopy, we quantified active cell movements during fusion. Inhibiting cytoskeletal contractility with Y-27632 Rho kinase inhibitor produced more granular tissues with fewer cell rearrangements but faster fusion. Further reducing contractility with blebbistatin and Y-27632 increased granularity, reduced rearrangements, and slowed fusion. Across all conditions, complete fusion coincided with frequent cell rearrangements. We present an active foam model representing cells as viscous shells with interfacial tension and persistent motility to link fusion outcomes and tissue fluidity to measurable cell properties. This framework shows how cell activity regulates tissue mechanics and offers insights for tissue assembly in regenerative medicine.</p>

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Active foam dynamics of tissue spheroid fusion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • Steven Ongenae,
  • Hanna Svitina,
  • Tom E. R. Belpaire,
  • Jef Vangheel,
  • Tobie Martens,
  • Pieter Vanden Berghe,
  • Ioannis Papantoniou,
  • Bart Smeets

摘要

Tissue spheroids fuse to form larger tissue structures, a process controlled by their living material properties. However, how these properties emerge from the active behavior of individual cells is not well understood. Here, we studied fusion dynamics of spheroids from human periosteum-derived cells. Using confocal microscopy, we measured spheroid granularity and, with two-photon microscopy, we quantified active cell movements during fusion. Inhibiting cytoskeletal contractility with Y-27632 Rho kinase inhibitor produced more granular tissues with fewer cell rearrangements but faster fusion. Further reducing contractility with blebbistatin and Y-27632 increased granularity, reduced rearrangements, and slowed fusion. Across all conditions, complete fusion coincided with frequent cell rearrangements. We present an active foam model representing cells as viscous shells with interfacial tension and persistent motility to link fusion outcomes and tissue fluidity to measurable cell properties. This framework shows how cell activity regulates tissue mechanics and offers insights for tissue assembly in regenerative medicine.