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Mechanical Role of Nesprin-1-Mediated Nucleus–Actin Filament Binding in Cyclic Stretch-Induced Fibroblast Elongation

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Abstract

The intracellular mechanical link tethering the nucleus to the cytoskeleton has been suggested to be the linker of the nucleoskeleton and cytoskeleton (LINC) complex. Previous studies have reported that knockdown of nesprin-1, a component of the LINC complex that directly binds to actin filaments, suppresses cellular morphological response to mechanical stimuli. The relation between nesprin-1 knockdown and cellular morphological changes, however, remains unclear. In this study, we examined the mechanical role of nucleus–actin filament binding in morphological changes of fibroblasts exposed to cyclic stretching. After exposure to 10% cyclic stretching for 6 h, fibroblasts transfected with nesprin-1-specific small interfering RNA showed fewer elongated shapes compared with non-transfected cells. To further examine the mechanical role of the nucleus and nucleus-bound actin filaments, we applied cyclic stretching to fibroblasts treated with Trichostatin A (TSA), which decreases nuclear stiffness and thereby reduces nucleus-binding actin filament tension. TSA-treatment was found to induce more rounded cellular shapes than those of non-treated cells under both static and cyclic stretching conditions. These results suggest that the tension of nucleus-bound actin filaments plays an important role in the formation of elongated fibroblasts under cyclic stretching and that nesprin-1 knockdown causes a decrease of tension in nucleus-associated actin filaments.

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Acknowledgments

The present study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Nos. 15K01304 and 16K15837) and the interdepartmental research fund of Kawasaki University of Medial Welfare.

Conflict of interest

N. Sakamoto, M. Ogawa, K. Sadamoto, M. Takeuchi, and N. Kataoka declare that they have no conflicts of interest.

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No human or animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Department of Intelligent Mechanical Systems, Graduate School of System Design, Tokyo Metropolitan University, 6-6 Asahigaoka, Hino, Tokyo, 191-0065, Japan

    Naoya Sakamoto

  2. Department of Medical Engineering, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki, Okayama, 701-0193, Japan

    Mai Ogawa, Kiyomi Sadamoto & Masaki Takeuchi

  3. Department of Mechanical Engineering, College of Engineering, Nihon University, 1 Nakagawara, Tokusada, Tamuramachi, Koriyama, Fukushima, 963-8642, Japan

    Noriyuki Kataoka

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  1. Naoya Sakamoto
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  2. Mai Ogawa
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  4. Masaki Takeuchi
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  5. Noriyuki Kataoka
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Correspondence to Naoya Sakamoto.

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Associate Editor Kris Noel Dahl oversaw the review of this article.

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Sakamoto, N., Ogawa, M., Sadamoto, K. et al. Mechanical Role of Nesprin-1-Mediated Nucleus–Actin Filament Binding in Cyclic Stretch-Induced Fibroblast Elongation. Cel. Mol. Bioeng. 10, 327–338 (2017). https://doi.org/10.1007/s12195-017-0487-6

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  • DOI: https://doi.org/10.1007/s12195-017-0487-6

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