20.500.12556/RUL-185957 Multi-phase field model reveals internal dissipation is crucial for spontaneous hole formation in cell monolayers Although cell monolayers typically remain confluent, they can spontaneously develop persistent holes as a result of collective cellular motion. Recent studies on MDCK monolayers cultured on soft substrates have revealed that cells can align to create regions of local nematic order, and topological defects that generate localised mechanical stresses which can spontaneously trigger hole formation. To investigate this process, we develop a continuum multi-phase field model that incorporates internal dissipation and active dipolar forces that drive cell shape anisotropy. Our simulations show that reducing substrate friction enhances cell-cell velocity correlations. In the low-friction regime, topological defects generate spiral flow patterns that concentrate stress and can trigger hole formation. By contrast, in the high-friction regime, holes do not nucleate. We further demonstrate that the number and stability of the holes—whether they close or persist—depends on both substrate friction and cellular activity, through a non-dimensional friction number. These findings highlight the importance of internal dissipation in modelling collective cell motion and the critical role of collective dynamics in maintaining tissue integrity. biological physics condensed matter physics statistical physics biofizika fizika kondenzirane snovi statistična fizika true false true Angleški jezik Slovenski jezik Članek v reviji 2026-08-24 14:48:46 2026-08-24 14:48:49 2026-08-25 04:18:07 0000-00-00 00:00:00 2026 0 0 8 str. art. no. 8288 Vol. 17 Jul. 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.3 2041-1723 10.1038/s41467-026-74977-y 288691459 https://www.nature.com/articles/s41467-026-74977-y 1 c3281336-9fb9-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244987 s41467-026-74977-y.pdf s41467-026-74977-y.pdf 1 B605D0E0C3A37D82FF9F0FC7AD62C617 b03c8d908bcb2902d6568f65c0def8011c30504b125f22b85bd49a2bac243afb fc1c34a0-9fb9-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244988 Fakulteta za matematiko in fiziko 0 0 0