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A nuclear jamming transition in vertebrate organogenesis

Nature Materials (2024)Cite this article

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Abstract

Jamming of cell collectives and associated rigidity transitions have been shown to play a key role in tissue dynamics, structure and morphogenesis. Cellular jamming is controlled by cellular density and the mechanics of cell–cell contacts. However, the contribution of subcellular organelles to the physical state of the emergent tissue is unclear. Here we report a nuclear jamming transition in zebrafish retina and brain tissues, where physical interactions between highly packed nuclei restrict cellular movements and control tissue mechanics and architecture. Computational modelling suggests that the nuclear volume fraction and anisotropy of cells control the emerging tissue physical state. Analysis of tissue architecture, mechanics and nuclear movements during eye development show that retina tissues undergo a nuclear jamming transition as they form, with increasing nuclear packing leading to more ordered cellular arrangements, reminiscent of the crystalline cellular packings in the functional adult eye. Our results reveal an important role of the cell nucleus in tissue mechanics and architecture.

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Fig. 1: Varying nuclear volume fraction and anisotropy in various zebrafish tissues.
Fig. 2: Characteristics of nuclear jamming for round nuclei.
Fig. 3: Nuclear jamming transition during zebrafish retina development.
Fig. 4: Retina INL tissue mechanics is controlled by nuclear mechanics.
Fig. 5: Nuclear jamming in retina and brain tissues leads to ordering of cellular packings.

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Data availability

The data supporting the findings of this study are included in the Article and its Supplementary Information files and are also available from the corresponding author upon request. Source data are provided with this paper.

Code availability

The simulation codes used in this Article are publicly available via GitHub at https://github.com/campaslab/active_foam_nucleus.

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Acknowledgements

We thank I. Lim, H. Lin and E. Sletten (University of California, Los Angeles) for sharing custom-made fluorinated dyes. We also thank C. Froeb for technical support, G. Stooke-Vaughan for her help and also for bringing the study of the retina to the Campas lab, M. Valet for her scientific advice and support and all the other Campas lab members for their help. We thank the Fish Facility of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) for their technical support, the MPI-CBG imaging facility (especially J. Peychl) for their advice and technical support on image acquisition and the MPI-CBG Transgenic core facility (J. Braumann and R. Naumann) for bevelling and spiking glass needles. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (R01HD095797 to O.C.), and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy–EXC 2068–390729961–Cluster of Excellence Physics of Life of TU Dresden. We acknowledge support from the UCSB Center for Scientific Computing from the CNSI, MRL: NSF MRSEC (DMR-1720256) and NSF CNS-1725797.

Author information

Author notes

  1. Sangwoo Kim

    Present address: Institute of Mechanical Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

  2. These authors contributed equally: Sangwoo Kim, Rana Amini.

Authors and Affiliations

  1. Department of Mechanical Engineering, University of California, Santa Barbara, CA, USA

    Sangwoo Kim & Otger Campàs

  2. Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany

    Rana Amini, Shuo-Ting Yen, Petr Pospíšil, Arthur Boutillon, Ilker Ali Deniz & Otger Campàs

  3. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

    Otger Campàs

  4. Center for Systems Biology Dresden, Dresden, Germany

    Otger Campàs

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Contributions

S.K., R.A. and O.C. designed the research. S.K. performed all the simulations. R.A. performed all the structural experiments and measurements of nuclear movements. R.A., S.-T.Y. and P.P. performed the mechanical measurements. A.B. and R.A. performed the laser ablation experiments. S.K., R.A., P.P., A.B. and I.A.D. analysed the data. S.K., R.A. and O.C. wrote the paper, with input from S.-T.Y., P.P. and A.B. O.C. supervised the project.

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Correspondence to Otger Campàs.

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Extended data

Extended Data Fig. 1 Effects of the magnitude of tension fluctuations on the nuclear jamming transition.

Dependence of long timescale MSRD values in terms of nuclear volume fraction for different magnitudes of tension fluctuations \(\Delta T/{T}_{0}\), showing that the dynamic slowdown in cell movements starts to occur at the same nuclear volume fraction (violet band) regardless of tension fluctuation strength. Error bands indicate standard deviation over N = 10 simulations.

Source data

Extended Data Fig. 2 Effects of nuclear stiffness on the nuclear jamming transition.

Dependence of the long timescale MSRD values (top) and neighbor exchange rate (bottom) for large nuclear volume fraction (\({\phi }_{N}=0.85\)) on the ratio of nuclear stiffness \({E}_{N}\) and the characteristic stress scale of cell deformations \({T}_{0}/{L}_{0}\). Large (small) values of \({E}_{N}/({T}_{0}/{L}_{0})\) indicate hard (soft) nuclei compared to the cell. Red lines are the values of long time MSRD and neighbor exchange rate for zero nuclear volume fraction (\({\phi }_{N}=0\)), and the vertical cyan dashed line indicates the point at which nuclear stiffness and the stress scale of cell deformations are equal, namely \({E}_{N}={T}_{0}/{L}_{0}\). Error bands indicate standard deviation over N = 10 simulations.

Source data

Extended Data Fig. 3 Schematic representation of the zebrafish retina before and after cell detachment from apical and basal tissue boundaries.

a, The zebrafish is a single-layered neuroepithelium with elongated cells connected to both the apical and basal tissue surfaces at 24 hpf. b, At approximately 40–42 hpf, majority of retinal cells detach from the tissue (apical and basal) boundaries and form a tissue with compact cells. This single-layered tissue eventually evolves into the different layers described in the main text (Fig. 3).

Source data

Extended Data Fig. 4 Tissue architecture during retina development: evolution of cell and nuclear shapes and sizes.

a-h, Top: schematic representation of cellular and nuclear architecture during different retinal stages (a, 24; b, 36; c, 55; e, 72; f, 92; g, 120 hpf). Bottom: Representative confocal sections of zebrafish retinae expressing the membrane marker (Tg(Bactin:HRAS-EGFP); orange) and nuclei marker Tg(h2az2a:h2az2a-mCherry); cyan). Scale bars, 20 μm. d, h, Higher magnification inset of the outlined region in (c), and (g) respectively. Scale bars, 10 μm.

Extended Data Fig. 5 Different brain regions show nuclear jamming.

Areas (a) and aspect ratios (b) of cells (orange) and nuclei (blue) in the MB (18 hpf) and OT (92 hpf). Their relative change between 18 to 92 hpf is plotted on the right panels. c, Nuclear volume fraction in the MB (18 hpf) and in the OT (92 hpf). Horizontal violet band shows the nuclear jamming volume fraction predicted theoretically (Fig. 2). d, Shape factor of cells (orange) and nuclei (blue) in the MB (18 hpf) and OT (92 hpf). Their relative change between 18 to 92 hpf is plotted on the right panels. MB (N = 6, n = 312), OT (N = 6, n = 419).

Supplementary information

Supplementary Information

Supplementary Notes 1–4.

Reporting Summary

Supplementary Video 1

Simulations of system dynamics for isotropic nuclei with varying nuclear volume fractions (φN = 0.20, 0.50 and 0.85 (from left to right)). Trajectories of 16 cells are shown in different colours.

Supplementary Video 2

Simulations of system dynamics for varying nuclear aspect ratios at large volume fractions (αN = 1, 2, 3 and 4 (from left to right); φN = 0.85). Trajectories of 16 cells are shown in different colours.

Supplementary Video 3

Representative video from a 4D time lapse of a 24 hpf retina of Tg(h2afz:GFP) embryo (nuclei, grey), overlaid with trajectories of 90 tracked nuclei. Time in h:min. Scale bar, 10 μm.

Supplementary Video 4

Representative video from a 4D time lapse of a 92 hpf retina of Tg(h2afz:GFP) embryo (nuclei, grey), overlaid with the trajectories of 90 tracked nuclei. Time in h:min. Scale bar, 10 μm.

Source data

Source Data Fig. 2

Source data for Fig. 2.

Source Data Fig. 3

Source data for Fig. 3.

Source Data Fig. 4

Source data for Fig. 4.

Source Data Fig. 5

Source data for Fig. 5.

Source Data Extended Data Fig. 1

Source data for Extended Data Fig. 1.

Source Data Extended Data Fig. 2

Source data for Extended Data Fig. 2.

Source Data Extended Data Fig. 3

Source data for Extended Data Fig. 3.

Source Data Extended Data Fig. 6

Source data for Extended Data Fig. 6.

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Kim, S., Amini, R., Yen, ST. et al. A nuclear jamming transition in vertebrate organogenesis. Nat. Mater. (2024). https://doi.org/10.1038/s41563-024-01972-3

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