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This study examines the finite Voronoi model, a computational approach for simulating non-confluent tissues where cells are not tightly packed together. The researchers discovered that the model exhibits unphysical behavior when simulating cell detachment and tissue fracture, with the timing of rupture events depending artificially on the computational time-step size due to a mathematical divergence in detachment forces. They developed a regularization method to fix this issue and showed that proper calibration of the model's detachment mechanics is critical for accurately predicting whether tissues will fracture or remain intact.
Why it matters
Understanding tissue detachment and fracture is important for studying wound healing, cancer metastasis, and embryonic development. This work provides essential corrections for computational models used to study these processes, ensuring that simulation results reflect actual biological physics rather than computational artifacts.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
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Abstract: Detachment and fracture are central to many tissue-level processes, but they are challenging to simulate with Voronoi-type models that typically assume a confluent tissue. Here we analyze the finite Voronoi model, a nonconfluent extension of conventional Voronoi models, in which cell boundaries are composed of straight Voronoi edges and circular arcs of fixed radius $ell$. When the line tension on cell-medium interfaces exceeds the tension on cell-cell contacts, we find that the model exhibits a strong time-step dependence in the fracture timescale of initially intact active clusters: decreasing $Delta t$ can unphysically suppress cluster rupture events. We trace this behavior to a divergence of detachment forces in the finite Voronoi model and introduce a simple regularization. We then compare the finite Voronoi model’s near-detachment mechanics to a deformable polygon model and propose two potential calibration strategies. Finally, we examine the fracture–no-fracture transition in nonconfluent tissues and show that it is governed by detachment mechanics: the calibration can even determine the sign of the transition’s dependence on cell shape. Our results show that, for studies focused on fracture or intercellular adhesion in nonconfluent monolayers, a physically motivated calibration of near-detachment mechanics in the finite Voronoi model is essential.
Source: Divergence of detachment forces in the finite Voronoi model