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Tracking intracellular forces and mechanical property changes in mouse one-cell embryo development



Cells comprise mechanically active matter that governs their functionality, but intracellular mechanics are difficult to study directly and are poorly understood. However, injected nanodevices open up opportunities to analyse intracellular mechanobiology. Here, we identify a programme of forces and changes to the cytoplasmic mechanical properties required for mouse embryo development from fertilization to the first cell division. Injected, fully internalized nanodevices responded to sperm decondensation and recondensation, and subsequent device behaviour suggested a model for pronuclear convergence based on a gradient of effective cytoplasmic stiffness. The nanodevices reported reduced cytoplasmic mechanical activity during chromosome alignment and indicated that cytoplasmic stiffening occurred during embryo elongation, followed by rapid cytoplasmic softening during cytokinesis (cell division). Forces greater than those inside muscle cells were detected within embryos. These results suggest that intracellular forces are part of a concerted programme that is necessary for development at the origin of a new embryonic life.

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Fig. 1: Fabricated nanodevices as intracellular sensors.
Fig. 2: ‘H-comb’ nanodevices detect mechanical loads inside mouse zygotes.
Fig. 3: Mechanics during the PM phase.
Fig. 4: Dynamic F-actin redistribution in mouse zygotes.
Fig. 5: Morphological and cytoskeletal changes during elongation and division.
Fig. 6: Tracking perturbation to the mechanical programme of mouse embryos.

Data availability

Supporting data are available in the Source Data files and from the corresponding authors upon reasonable request.


  1. 1.

    Kollmannsberger, P. & Fabry, B. Linear and nonlinear rheology of living cells. Ann. Rev. Mat. Res. 41, 75–97 (2011).

    CAS  Google Scholar 

  2. 2.

    Guo, M. et al. Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy. Cell 158, 822–832 (2014).

    CAS  Google Scholar 

  3. 3.

    Davidson, L., von Dassow, M. & Zhou, J. Multi-scale mechanics from molecules to morphogenesis. Int. J. Biochem. Cell Biol. 41, 2147–2162 (2009).

    CAS  Google Scholar 

  4. 4.

    Savin, T. et al. On the growth and form of the gut. Nature 476, 57–62 (2011).

    CAS  Google Scholar 

  5. 5.

    Farge, E. Mechanical induction of Twist in the Drosophila foregut/stomodeal primordium. Curr. Biol. 13, 1365–1377 (2003).

    CAS  Google Scholar 

  6. 6.

    Kahn, J. et al. Muscle contraction is necessary to maintain joint progenitor cell fate. Dev. Cell 16, 734–743 (2009).

    CAS  Google Scholar 

  7. 7.

    Mammoto, A., Mammoto, T. & Ingber, D. E. Mechanosensitive mechanisms in transcriptional regulation. J. Cell Sci. 125, 3061–3073 (2012).

    CAS  Google Scholar 

  8. 8.

    Chen, D. T. N., Wen, Q., Janmey, P. A., Crocker, J. C. & Yodh, A. G. Rheology of soft materials. Ann. Rev. Condens. Matter Phys. 1, 301–322 (2010).

    CAS  Google Scholar 

  9. 9.

    Moeendarbary, E. et al. The cytoplasm of living cells behaves as a poroelastic material. Nat. Mater. 12, 253–261 (2013).

    CAS  Google Scholar 

  10. 10.

    Roca-Cusachs, P., Conte, V. & Trepat, X. Quantifying forces in cell biology. Nat. Cell Biol. 19, 742–751 (2017).

    CAS  Google Scholar 

  11. 11.

    Bao, G. & Suresh, S. Cell and molecular mechanics of biological materials. Nat. Mater. 2, 715–725 (2003).

    CAS  Google Scholar 

  12. 12.

    Lim, C. T., Zhou, E. H. & Quek, S. T. Mechanical models for living cells—a review. J. Biomech. 39, 195–216 (2006).

    CAS  Google Scholar 

  13. 13.

    Trepat, X. et al. Universal physical responses to stretch in the living cell. Nature 447, 592–595 (2007).

    CAS  Google Scholar 

  14. 14.

    Polacheck, W. J. & Chen, C. S. Measuring cell-generated forces: a guide to the available tools. Nat. Methods 13, 415–423 (2016).

    CAS  Google Scholar 

  15. 15.

    Trepat, X., Lenormand, G. & Fredberg, J. J. Universality in cell mechanics. Soft Mat. 4, 1750–1759 (2008).

    CAS  Google Scholar 

  16. 16.

    Keren, K., Yam, P. T., Kinkhabwala, A., Mogilner, A. & Theriot, J. A. Intracellular fluid flow in rapidly moving cells. Nat. Cell Biol. 11, 1219–1224 (2009).

    CAS  Google Scholar 

  17. 17.

    Zimmerman, J. F. et al. Free-standing kinked silicon nanowires for probing inter- and intracellular force dynamics. Nano Lett. 15, 5492–5498 (2015).

    CAS  Google Scholar 

  18. 18.

    Hendricks, A. G. & Goldman, Y. E. Measuring molecular forces using calibrated optical tweezers in living cells. Methods Mol. Biol. 1486, 537–552 (2017).

    Google Scholar 

  19. 19.

    Gómez-Martínez, R. et al. Silicon chips detect intracellular pressure changes in living cells. Nat. Nanotechnol. 8, 517–521 (2013).

    Google Scholar 

  20. 20.

    Torras, N. et al. Suspended planar-array chips for molecular multiplexing at the microscale. Adv. Mater. 28, 1449–1454 (2016).

    CAS  Google Scholar 

  21. 21.

    Discher, D. E., Mooney, D. J. & Zandstra, P. W. Growth factors, matrices, and forces combine and control stem cells. Science 26, 1673–1677 (2009).

    Google Scholar 

  22. 22.

    Lutolf, M. P., Gilbert, P. M. & Blau, H. M. Designing materials to direct stem-cell fate. Nature 462, 433–441 (2009).

    CAS  Google Scholar 

  23. 23.

    Maître, J. L., Niwayama, R., Turlier, H., Nédélec, F. & Hiiragi, T. Pulsatile cell-autonomous contractility drives compaction in the mouse embryo. Nat. Cell Biol. 17, 849–855 (2015).

    Google Scholar 

  24. 24.

    Lehtonen, E. Changes in cell dimensions and intercellular contacts during cleavage-stage cell cycles in mouse embryonic cells. J. Embryol. Exp. Morphol. 58, 231–249 (1980).

    CAS  Google Scholar 

  25. 25.

    Tzur, A., Kafri, R., LeBleu, V. S., Lahav, G. & Kirschner, M. W. Cell growth and size homeostasis in proliferating animal cells. Science 325, 167–171 (2009).

    CAS  Google Scholar 

  26. 26.

    Zhou, L. & Dean, J. Reprogramming the genome to totipotency in mouse embryos. Trends Cell Biol. 25, 82–91 (2015).

    CAS  Google Scholar 

  27. 27.

    Campàs, O. et al. Quantifying cell-generated mechanical forces within living embryonic tissues. Nat. Methods 11, 183–189 (2014).

    Google Scholar 

  28. 28.

    Hyman, A. A., Weber, C. A. & Jülicher, F. Liquid-liquid phase separation in biology. Ann. Rev. Cell Dev. Biol. 30, 39–58 (2014).

    CAS  Google Scholar 

  29. 29.

    Yoshida, N., Brahmajosyula, M., Shoji, S., Amanai, M. & Perry, A. C. F. Epigenetic discrimination by mouse metaphase II oocytes mediates asymmetric chromatin remodeling independently of meiotic exit. Dev. Biol. 301, 464–477 (2007).

    CAS  Google Scholar 

  30. 30.

    Suzuki, T. et al. Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes. Nat. Commun. 7, 12676 (2016).

    CAS  Google Scholar 

  31. 31.

    Rai, A. K., Rai, A., Ramaiya, A. J., Jha, R. & Mallik, R. Molecular adaptations allow dynein to generate large collective forces inside cells. Cell 152, 172–182 (2013).

    CAS  Google Scholar 

  32. 32.

    Payne, C., Rawe, V., Ramalho-Santos, J., Simerly, C. & Schatten, G. Preferentially localized dynein and perinuclear dynactin associate with nuclear pore complex proteins to mediate genomic union during mammalian fertilization. J. Cell Sci. 116, 4727–4738 (2003).

    CAS  Google Scholar 

  33. 33.

    Chaigne, A. et al. F-actin mechanics control spindle centring in the mouse zygote. Nat. Commun. 7, 10253 (2016).

    CAS  Google Scholar 

  34. 34.

    Rowat, A. C., Lammerding, J. & Ipsen, J. H. Mechanical properties of the cell nucleus and the effect of emerin deficiency. Biophys. J. 91, 4649–4664 (2006).

    CAS  Google Scholar 

  35. 35.

    Hose, BasarabG. et al. Reversible disassembly of the actin cytoskeleton improves the survival rate and developmental competence of cryopreserved mouse oocytes. PLoS ONE 3, e2787 (2008).

    Google Scholar 

  36. 36.

    Sutovsky, P., Simerly, C., Hewitson, L. & Schatten, G. Assembly of nuclear pore complexes and annulate lamellae promotes normal pronuclear development in fertilized mammalian oocytes. J. Cell Sci. 111, 2841–2854 (1998).

    CAS  Google Scholar 

  37. 37.

    Chew, T. G., Lorthongpanich, C., Ang, W. X., Knowles, B. B. & Solter, D. Symmetric cell division of the mouse zygote requires an actin network. Cytoskeleton 69, 1040–1046 (2012).

    CAS  Google Scholar 

  38. 38.

    Yu, X. J. et al. The subcortical maternal complex controls symmetric division of mouse zygotes by regulating F-actin dynamics. Nat. Commun. 5, 4887 (2014).

    CAS  Google Scholar 

  39. 39.

    Schatten, G., Simerly, C. & Schatten, H. Microtubule configurations during fertilization, mitosis, and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization. Proc. Natl Acad. Sci. USA 82, 4152–4156 (1985).

    CAS  Google Scholar 

  40. 40.

    Zenker, J. et al. A microtubule-organizing center directing intracellular transport in the early mouse embryo. Science 357, 925–928 (2017).

    CAS  Google Scholar 

  41. 41.

    Ajduk, A. et al. Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability. Nat. Commun. 2, 417 (2011).

    Google Scholar 

  42. 42.

    Schäfer, A. Influence of myosin II activity on stiffness of fibroblast cells. Acta Biomater. 1, 273–280 (2005).

    Google Scholar 

  43. 43.

    Strom, A. R. et al. Phase separation drives heterochromatin domain formation. Nature 547, 241–245 (2017).

    CAS  Google Scholar 

  44. 44.

    Larson, A. G. et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547, 236–240 (2017).

    CAS  Google Scholar 

  45. 45.

    Quinn, P., Barros, C. & Whittingham, D. G. Preservation of hamster oocytes to assay the fertilizing capacity of human spermatozoa. J. Reprod. Fertil. 66, 161–168 (1982).

    CAS  Google Scholar 

  46. 46.

    Shoji, S. et al. Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20. EMBO J. 25, 834–845 (2006).

    CAS  Google Scholar 

  47. 47.

    Yoshida, N. & Perry, A. C. F. Piezo-actuated mouse intracytoplasmic sperm injection (ICSI). Nat. Protoc. 2, 296–304 (2007).

    CAS  Google Scholar 

  48. 48.

    Perry, A. C. F., Wakayama, T., Cooke, I. M. & Yanagimachi, R. Mammalian oocyte activation by the synergistic action of discrete sperm head components: induction of calcium transients and involvement of proteolysis. Dev. Biol. 217, 386–393 (2000).

    CAS  Google Scholar 

  49. 49.

    Suzuki, T., Asami, M. & Perry, A. C. F. Asymmetric parental genome engineering by Cas9 during mouse meiotic exit. Sci. Rep. 4, 7621 (2014).

    CAS  Google Scholar 

  50. 50.

    Burkel, B. M., von Dassow, G. & Bement, W. M. Versatile fluorescent probes for actin filaments based on the actin-binding domain of utrophin. Cell Motil. Cytoskeleton 64, 822–832 (2007).

    CAS  Google Scholar 

  51. 51.

    Suzuki, T. et al. Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase. Development 137, 3281–3291 (2010).

    CAS  Google Scholar 

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We are grateful to B. Nichols, J. Campos, T. Suárez and C. Tickle for their constructive comments during manuscript preparation and thank Animal Facility support staff for ensuring the welfare of animals used in this work. We are deeply indebted to the late Dino Sharma for help with image collection. We acknowledge support to A.C.F.P. from the Medical Research Council, UK (grant nos. G1000839, MR/N000080/1 and MR/N020294/1) and the Biology and Biological Science Research Council, UK (grant no. BB/P009506/1) and to J.A.P from the Spanish Government, grant nos. TEC2014-51940-C2 and TEC2017-85059-C3 with Feder funding. We also thank the clean room staff of IMB-CNM for assistance with chip fabrication.

Author information




A.C.F.P. and J.A.P. conceived core experiments. M.D., R.G.-M. and J.A.P. performed nanodevice fabrication, T.S. and M.A. performed microinjection and embryo production and M.A. and M.D.V. undertook image collection. Data analysis and modelling were by N.T., M.A., M.I.A., R.C. and J.A.P. A.C.F.P. and J.A.P. wrote most of the manuscript with contributions from the other authors.

Corresponding authors

Correspondence to José Antonio Plaza or Anthony C. F. Perry.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–17, Videos 1–9, discussion, methods and references.

Reporting Summary

Supplementary Video 1

Animation of the axis of rotation of the nanodevice.

Supplementary Video 2

Brightfield video of mouse zygote during PM.

Supplementary Video 3

Brightfield video of mouse zygote containing microsphere

Supplementary Video 4

Tracking particle migration within an embryo.

Supplementary Video 5

Dynamic surface plot of Utr-mCherry in mouse embryos.

Supplementary Video 6

Fluorescence in mouse embryos containing Utr-mCherry.

.Supplementary Video 7

Brightfield video of mouse embryo containing 25-nm ‘H-comb’ nanodevice

Supplementary Video 8

Brightfield video of ‘scary spider’ mouse embryo containing 25-nm ‘H-comb’ nanodevice

Supplementary Video 9

The effect of actomyosin inhibition is consistent with the GES model.

Source data

Source Data Fig. 1

Statistical source data

Source Data Fig. 2

Statistical source data

Source Data Fig. 3

Statistical source data

Source Data Fig. 4

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Source Data Fig. 5

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Source Data Fig. 6

Statistical source data

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Duch, M., Torras, N., Asami, M. et al. Tracking intracellular forces and mechanical property changes in mouse one-cell embryo development. Nat. Mater. 19, 1114–1123 (2020).

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