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The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization

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Abstract

Physical cues play a fundamental role in a wide range of biological processes, such as embryogenesis, wound healing, tumour invasion and connective tissue morphogenesis. Although it is well known that during these processes, cells continuously interact with the local extracellular matrix (ECM) through cell traction forces, the role of these mechanical interactions on large scale cellular and matrix organization remains largely unknown. In this study, we use a simple theoretical model to investigate cellular and matrix organization as a result of mechanical feedback signals between cells and the surrounding ECM. The model includes bi-directional coupling through cellular traction forces to deform the ECM and through matrix deformation to trigger cellular migration. In addition, we incorporate the mechanical contribution of matrix fibres and their reorganization by the cells. We show that a group of contractile cells will self-polarize at a large scale, even in homogeneous environments. In addition, our simulations mimic the experimentally observed alignment of cells in the direction of maximum stiffness and the building up of tension as a consequence of cell and fibre reorganization. Moreover, we demonstrate that cellular organization is tightly linked to the mechanical feedback loop between cells and matrix. Cells with a preference for stiff environments have a tendency to form chains, while cells with a tendency for soft environments tend to form clusters. The model presented here illustrates the potential of simple physical cues and their impact on cellular self-organization. It can be used in applications where cell-matrix interactions play a key role, such as in the design of tissue engineering scaffolds and to gain a basic understanding of pattern formation in organogenesis or tissue regeneration.

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Acknowledgments

This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft; DU298/14-1).

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Authors and Affiliations

  1. Julius Wolff Institute, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinkum, Institutsgebäude Süd/Südstraße 2, Augustenburger Platz 1, 13353 , Berlin, Germany

    Sara Checa, Ansgar Petersen & Georg N. Duda

  2. Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Georg N. Duda

  3. Berlin Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Ansgar Petersen & Georg N. Duda

  4. Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Sara Checa, Ansgar Petersen & Georg N. Duda

  5. Department of Mechanical Engineering, Stanford University, California, CA, USA

    Manuel K. Rausch & Ellen Kuhl

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  1. Sara Checa
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  2. Manuel K. Rausch
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Correspondence to Sara Checa.

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Checa, S., Rausch, M.K., Petersen, A. et al. The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization. Biomech Model Mechanobiol 14, 1–13 (2015). https://doi.org/10.1007/s10237-014-0581-9

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  • DOI: https://doi.org/10.1007/s10237-014-0581-9

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