A homeostatic role of nucleus-actin filament coupling in the regulation of cellular traction forces in fibroblasts

doi:10.1007/s10237-024-01839-1

. 2024 Aug;23(4):1289-1298.

doi: 10.1007/s10237-024-01839-1. Epub 2024 Mar 19.

A homeostatic role of nucleus-actin filament coupling in the regulation of cellular traction forces in fibroblasts

Naoya Sakamoto^{1

2}, Keisuke Ito³, Satoshi Ii^{3

4}, Daniel E Conway⁵, Yuki Ueda³, Jiro Nagatomi^{4

6}

Affiliations

¹ Department of Mechanical Systems Engineering, Tokyo Metropolitan University, Minami- Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan. sakan@tmu.ac.jp.
² Research Center for Medicine-Engineering Collaboration, Tokyo Metropolitan University, Minami-Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan. sakan@tmu.ac.jp.
³ Department of Mechanical Systems Engineering, Tokyo Metropolitan University, Minami- Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan.
⁴ Research Center for Medicine-Engineering Collaboration, Tokyo Metropolitan University, Minami-Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan.
⁵ Department of Biomedical Engineering, The Ohio State University, 140W 19th Avenue, Columbus, OH, USA.
⁶ Department of Bioengineering, Clemson University, 301 Rhodes Research Center, Clemson, SC, 29634-0905, USA.

PMID: 38502433
DOI: 10.1007/s10237-024-01839-1

A homeostatic role of nucleus-actin filament coupling in the regulation of cellular traction forces in fibroblasts

Naoya Sakamoto et al. Biomech Model Mechanobiol. 2024 Aug.

. 2024 Aug;23(4):1289-1298.

doi: 10.1007/s10237-024-01839-1. Epub 2024 Mar 19.

Authors

Naoya Sakamoto^{1

2}, Keisuke Ito³, Satoshi Ii^{3

4}, Daniel E Conway⁵, Yuki Ueda³, Jiro Nagatomi^{4

6}

Affiliations

¹ Department of Mechanical Systems Engineering, Tokyo Metropolitan University, Minami- Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan. sakan@tmu.ac.jp.
² Research Center for Medicine-Engineering Collaboration, Tokyo Metropolitan University, Minami-Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan. sakan@tmu.ac.jp.
³ Department of Mechanical Systems Engineering, Tokyo Metropolitan University, Minami- Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan.
⁴ Research Center for Medicine-Engineering Collaboration, Tokyo Metropolitan University, Minami-Osawa 1-1, Hachioji, Tokyo, 192-0397, Japan.
⁵ Department of Biomedical Engineering, The Ohio State University, 140W 19th Avenue, Columbus, OH, USA.
⁶ Department of Bioengineering, Clemson University, 301 Rhodes Research Center, Clemson, SC, 29634-0905, USA.

PMID: 38502433
DOI: 10.1007/s10237-024-01839-1

Abstract

Cellular traction forces are contractile forces that depend on the material/substrate stiffness and play essential roles in sensing mechanical environments and regulating cell morphology and function. Traction forces are primarily generated by the actin cytoskeleton and transmitted to the substrate through focal adhesions. The cell nucleus is also believed to be involved in the regulation of this type of force; however, the role of the nucleus in cellular traction forces remains unclear. In this study, we explored the effects of nucleus-actin filament coupling on cellular traction forces in human dermal fibroblasts cultured on substrates with varying stiffness (5, 15, and 48 kPa). To investigate these effects, we transfected the cells with a dominant-negative Klarsicht/ANC-1/Syne homology (DN-KASH) protein that was designed to displace endogenous linker proteins and disrupt nucleus-actin cytoskeleton connections. The force that exists between the cytoskeleton and the nucleus (nuclear tension) was also evaluated with a fluorescence resonance energy transfer (FRET)-based tension sensor. We observed a biphasic change in cellular traction forces with a peak at 15 kPa, regardless of DN-KASH expression, that was inversely correlated with the nuclear tension. In addition, the relative magnitude and distribution of traction forces in nontreated wild-type cells were similar across different stiffness conditions, while DN-KASH-transfected cells exhibited a different distribution pattern that was impacted by the substrate stiffness. These results suggest that the nucleus-actin filament coupling play a homeostatic role by maintaining the relative magnitude of cellular traction forces in fibroblasts under different stiffness conditions.

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References

1. Achterberg VF et al (2014) The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function. J Invest Dermatol 134:1862–1872. https://doi.org/10.1038/jid.2014.90 - DOI
1. Ambrosi D, Duperray A, Peschetola V, Verdier C (2009) Traction patterns of tumor cells. J Math Biol 58:163–181. https://doi.org/10.1007/s00285-008-0167-1 - DOI
1. Anno T, Sakamoto N, Sato M (2012) Role of nesprin-1 in nuclear deformation in endothelial cells under static and uniaxial stretching conditions Biochem. Biophys Res Commun 424:94–99. https://doi.org/10.1016/j.bbrc.2012.06.073 - DOI
1. Arsenovic PT et al (2016) Nesprin-2G, a component of the Nuclear LINC Complex, is subject to myosin-dependent tension. Biophys J 110:34–43. https://doi.org/10.1016/j.bpj.2015.11.014 - DOI
1. Booth-Gauthier EA, Du V, Ghibaudo M, Rape AD, Dahl KN, Ladoux B (2013) Hutchinson-Gilford progeria syndrome alters nuclear shape and reduces cell motility in three dimensional model substrates. Integr Biol (Camb) 5:569–577. https://doi.org/10.1039/c3ib20231c - DOI

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[1] Achterberg VF et al (2014) The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function. J Invest Dermatol 134:1862–1872. https://doi.org/10.1038/jid.2014.90 - DOI

[2] Achterberg VF et al (2014) The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function. J Invest Dermatol 134:1862–1872. https://doi.org/10.1038/jid.2014.90 - DOI

[3] Ambrosi D, Duperray A, Peschetola V, Verdier C (2009) Traction patterns of tumor cells. J Math Biol 58:163–181. https://doi.org/10.1007/s00285-008-0167-1 - DOI

[4] Ambrosi D, Duperray A, Peschetola V, Verdier C (2009) Traction patterns of tumor cells. J Math Biol 58:163–181. https://doi.org/10.1007/s00285-008-0167-1 - DOI

[5] Anno T, Sakamoto N, Sato M (2012) Role of nesprin-1 in nuclear deformation in endothelial cells under static and uniaxial stretching conditions Biochem. Biophys Res Commun 424:94–99. https://doi.org/10.1016/j.bbrc.2012.06.073 - DOI

[6] Anno T, Sakamoto N, Sato M (2012) Role of nesprin-1 in nuclear deformation in endothelial cells under static and uniaxial stretching conditions Biochem. Biophys Res Commun 424:94–99. https://doi.org/10.1016/j.bbrc.2012.06.073 - DOI

[7] Arsenovic PT et al (2016) Nesprin-2G, a component of the Nuclear LINC Complex, is subject to myosin-dependent tension. Biophys J 110:34–43. https://doi.org/10.1016/j.bpj.2015.11.014 - DOI

[8] Arsenovic PT et al (2016) Nesprin-2G, a component of the Nuclear LINC Complex, is subject to myosin-dependent tension. Biophys J 110:34–43. https://doi.org/10.1016/j.bpj.2015.11.014 - DOI

[9] Booth-Gauthier EA, Du V, Ghibaudo M, Rape AD, Dahl KN, Ladoux B (2013) Hutchinson-Gilford progeria syndrome alters nuclear shape and reduces cell motility in three dimensional model substrates. Integr Biol (Camb) 5:569–577. https://doi.org/10.1039/c3ib20231c - DOI

[10] Booth-Gauthier EA, Du V, Ghibaudo M, Rape AD, Dahl KN, Ladoux B (2013) Hutchinson-Gilford progeria syndrome alters nuclear shape and reduces cell motility in three dimensional model substrates. Integr Biol (Camb) 5:569–577. https://doi.org/10.1039/c3ib20231c - DOI

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A homeostatic role of nucleus-actin filament coupling in the regulation of cellular traction forces in fibroblasts

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A homeostatic role of nucleus-actin filament coupling in the regulation of cellular traction forces in fibroblasts

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