ArticlePNAS nexus2025
Confinement in fibrous environments positions and orients mitotic spindles.
Article in PNAS nexus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Efficient spatio-angular reconstruction enables high-fidelity mapping of six-dimensional structures and dynamics with polarized fluorescence microscopy.Nature communications · 2026Article
- The physical properties of ascitic fluid enhance metastatic potential by inducing mitotic abnormalities and multinucleation in ovarian cancer.BMC cancer · 2026Article
- Deep learning reveals how cells pull, buckle, and navigate fibrous environments.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Observing biological spatio-angular structures and dynamics with statistical image reconstruction and polarized fluorescence microscopy.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
Accurate positioning of the mitotic spindle within the rounded cell body is critical to physiological maintenance. Mitotic cells encounter confinement from neighboring cells or the extracellular matrix (ECM), which can cause rotation of mitotic spindles and tilting of the metaphase plate (MP). To understand the effect of confinement on mitosis by fibers (ECM confinement), we use flexible ECM-mimicking nanofibers that allow natural rounding of the cell body while confining it to differing levels. Rounded mitotic bodies are anchored in place by actin retraction fibers (RFs) originating from adhesions on fibers. We discover that the extent of confinement influences RF organization in 3D, forming triangular and band-like patterns on the cell cortex under low and high confinement, respectively. Our mechanistic analysis reveals that the patterning of RFs on the cell cortex is the primary driver of the MP rotation. A stochastic Monte Carlo simulation of the centrosome, chromosome, membrane interactions, and 3D arrangement of RFs recovers MP tilting trends observed experimentally. Under high ECM confinement, the fibers can mechanically pinch the cortex, causing the MP to have localized deformations at contact sites with fibers. Interestingly, high ECM confinement leads to low and high MP tilts, which we mechanistically show to depend upon the extent of cortical deformation, RF patterning, and MP position. We identify that cortical deformation and RFs work in tandem to limit MP tilt, while asymmetric positioning of MP leads to high tilts. Overall, we provide fundamental insights into how mitosis may proceed in ECM-confining microenvironments in vivo.
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Registered trials
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