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Collective transitions from orbiting to matrix invasion in three-dimensional multicellular spheroids
Jiwon Kim1, Hyuntae Jeong1, Carles Falcó2
1School of Engineering, Legoretta Cancer Center. Brown University. 184 Hope St Box D, Providence RI 02912, USA.
Nature Physics
|February 23, 2026
Summary
Epithelial cell spheroids transition from orbiting to radial invasion by interacting with matrix curvature. This process, crucial for tissue morphogenesis and tumor progression, can be modulated by osmotic pressure.
Area of Science:
- Cell biology
- Biophysics
- Developmental biology
Background:
- Tissue sculpting into spherical shapes involves coordinated cell rotation and matrix remodeling.
- Symmetry-breaking transitions in epithelial tissues are driven by cell-matrix interactions but are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms of symmetry-breaking transitions in epithelial spheroids.
- To investigate the role of matrix curvature in collective cell migration and invasion.
- To explore methods for controlling tissue morphogenesis.
Main Methods:
- Live imaging of epithelial cell spheroids on curved matrix interfaces.
- Analysis of cell-matrix interactions, contractile tractions, and collagen fiber alignment.
- Manipulation of osmotic pressure to influence spheroid behavior.
Main Results:
- Epithelial spheroids transition from circumferential orbiting to radial invasion, influenced by matrix curvature.
- Sharper matrix curvature enhances contractile tractions, aligning collagen fibers radially.
- Invasion is primed by initial spheroid morphology and can be reversed by osmotic pressure.
Conclusions:
- Collective cell migration and matrix curvature interplay to govern symmetry-breaking in tissue morphogenesis.
- Findings have implications for understanding embryonic development and tumor invasion.
- Modulating cell-matrix interactions offers potential for controlling tissue development and disease progression.
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