Active foam dynamics of tissue spheroid fusion

Steven Ongenae, Hanna Svitina, Tom E. R. Belpaire, Jef Vangheel, Tobie Martens, Pieter Vanden Berghe, Ioannis Papantoniou and Bart Smeets ()
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Steven Ongenae: KU Leuven, MeBioS, Department of Biosystems
Hanna Svitina: KU Leuven, Prometheus, Division of Skeletal Tissue Engineering
Tom E. R. Belpaire: KU Leuven, MeBioS, Department of Biosystems
Jef Vangheel: KU Leuven, MeBioS, Department of Biosystems
Tobie Martens: KU Leuven, Cell & tissue Imaging Core
Pieter Vanden Berghe: KU Leuven, Cell & tissue Imaging Core
Ioannis Papantoniou: KU Leuven, Prometheus, Division of Skeletal Tissue Engineering
Bart Smeets: KU Leuven, MeBioS, Department of Biosystems

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-65463-y

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