Speaker
Description
Epithelial tissues maintain structural integrity through a balance between cell-cell adhesion and cortical contractility. Disruption of E-cadherin-mediated adhesion is a hallmark of metastatic progression, yet the physical mechanisms by which local molecular defects escalate into global tissue destabilization remain poorly understood. Traditional theoretical studies have focused on the density of defective cells, while largely neglecting their spatial organization—a critical factor in clonal expansion.We employ a 2D stochastic vertex model to investigate how the spatial arrangement of adhesion-deficient cells dictates tissue-scale rigidity transitions. By comparing random and clustered distributions, we identify a distinct mechanical response across scales. Our results show that while isolated defects are rapidly eliminated via $T_2$ extrusion events with minimal impact on tissue architecture, clustered defects significantly delay extrusion kinetics. This "shielding effect" fosters the emergence of local fluidization zones characterized by a high cellular shape index ($q > 3.81$). Furthermore, we demonstrate that clustered defects leave a "topological scar" in the wild-type matrix, lowering the global threshold for the unjamming transition. By linking local molecular dysfunction to macroscopic fluidization, our framework provides new insights into how clonal clustering facilitates tissue invasion and metastasis.
Bibliography
@article{Bi2015,
author = {Bi, D. and Lopez, J. H. and Schwarz, J. M. and Manning, M. L.},
title = {A density-independent rigidity transition in biological tissues},
journal = {Nature Physics},
volume = {11},
pages = {1074--1079},
year = {2015}
}
@article{Park2015,
author = {Park, J.-A. and et al.},
title = {Unjamming and cell shape in the asthmatic airway epithelium},
journal = {Nature Materials},
volume = {14},
pages = {1040--1048},
year = {2015}
}
@article{Alt2017,
author = {Alt, S. and Ganguly, P. and Salbreux, G.},
title = {Vertex models: from cell mechanics to tissue morphogenesis},
journal = {Philosophical Transactions of the Royal Society B},
volume = {372},
pages = {20150520},
year = {2017}
}
@article{Mestre2016,
author = {Mestre, T. and et al.},
title = {Quantification of topological features in cell meshes to explore E-cadherin dysfunction},
journal = {Scientific Reports},
volume = {6},
pages = {25101},
year = {2016}
}
@article{Briñas2024,
author = {Briñas-Pascual, N. and Manso, V. and Guerrero, P.},
title = {Spatial organisation of adhesion-deficient cells controls epithelial rigidity transitions},
journal = {Preprint / In preparation},
year = {2024}
}
