Oriented cell division is fundamental to development and tissue organization, requiring precise control of both spindle positioning and orientation. While cortical pulling forces mediated by dynein motor proteins are well-established drivers of spindle dynamics, the contribution of microtubule polymerization-based pushing forces remains unclear. We developed a generalizable computational biophysical model that integrates both pulling and pushing mechanisms to investigate spindle behavior across diverse cell types and geometries. This model successfully recapitulates experimental observations in three well-studied models:Drosophilafollicular epithelial cells,Drosophilaneuroblasts, and the earlyC. elegansembryo. Systematic analysis reveals that while pulling forces are the primary drivers of directed spindle orientation, pushing forces play crucial supporting roles by preventing spindle stalling and promoting alignment dynamics, particularly at high initial misalignment angles. We further applied our model to irregularly shaped zebrafish endothelial cells, which present unique challenges due to their non-spherical morphology and dynamic shape changes during mitosis. Our results demonstrate that asymmetric cortical force generator distributions, potentially localized at cell-cell junctions, can account for the observed off-center spindle positioning in these cells. This work provides a unified framework for understanding how the interplay between cell geometry, molecular polarity cues, and competing physical forces determines spindle dynamics, offering new insights into both canonical and non-canonical division orientations across cell types.
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Mechanical feedback controls the emergence of dynamical memory in growing tissue monolayers
The growth of a tissue, which depends on cell–cell interactions and biologically relevant processes such as cell division and apoptosis, is regulated by a mechanical feedback mechanism. We account for these effects in a minimal two-dimensional model in order to investigate the consequences of mechanical feedback, which is controlled by a critical pressure, p c . A cell can only grow and divide if its pressure, due to interaction with its neighbors, is less than p c . Because temperature is not a relevant variable, the cell dynamics is driven by self-generated active forces (SGAFs) that arise due to cell division. We show that even in the absence of intercellular interactions, cells undergo diffusive behavior. The SGAF-driven diffusion is indistinguishable from the well-known dynamics of a free Brownian particle at a fixed finite temperature. When intercellular interactions are taken into account, we find persistent temporal correlations in the force–force autocorrelation function (FAF) that extends over a timescale of several cell division times. The time-dependence of the FAF reveals memory effects, which increases as p c increases. The observed non-Markovian effects emerge due to the interplay of cell division and mechanical feedback and are inherently a non-equilibrium phenomenon.
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- Award ID(s):
- 2014141
- PAR ID:
- 10424675
- Date Published:
- Journal Name:
- The Journal of Chemical Physics
- Volume:
- 156
- Issue:
- 24
- ISSN:
- 0021-9606
- Page Range / eLocation ID:
- 245101
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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