Transient active force generation and stress fibre remodelling in cells under cyclic loading
The active cytoskeleton is known to play an important mechanistic role in cellular structure, spreading, and contractility. Contractility is actively generated by stress fibres (SF), which continuously remodel in response to physiological dynamic loading conditions. The influence of actin-myosin cross-bridge cycling on SF remodelling under dynamic loading conditions has not previously been uncovered. In this study, a novel SF cross-bridge cycling model is developed to predict transient active force generation in cells subjected to dynamic loading. Rates of formation of cross-bridges within SFs are governed by the chemical potentials of attached and unattached myosin heads. This transient cross-bridge cycling model is coupled with a thermodynamically motivated framework for SF remodelling to analyse the influence of transient force generation on cytoskeletal evolution. A 1D implementation of the model is shown to correctly predict complex patterns of active cell force generation under a range of dynamic loading conditions, as reported in previous experimental studies.
KeywordsActive cell force generation Dynamic contractility Stress fibre remodelling Cross-bridge cycling Computational cell mechanics
Funding support was provided by the Irish Research Council (IRC) postgraduate scholarship (GOIPG/2015/2954), the National University of Ireland Galway Hardiman scholarship, and the Science Foundation Ireland (SFI-12/IP/1723). The authors would like to acknowledge the Irish Centre for High-End Computing (ICHEC) for provision of computational facilities and support.
- Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell. Garland Science, New YorkGoogle Scholar
- Curtin NA, Davies RE (1975) Very high tension with very little ATP breakdown by active skeletal muscle. J Mechanochem Cell Motil 3(2):147–154Google Scholar
- Dowling EP, Ronan W, Ofek G, Deshpande VS, McMeeking RM, Athanasiou KA, McGarry JP (2012) The effect of remodelling and contractility of the actin cytoskeleton on the shear resistance of single cells: a computational and experimental investigation. J R Soc Interface R Soc 9(77):3469–3479. https://doi.org/10.1098/rsif.2012.0428 CrossRefGoogle Scholar
- Foolen J, Deshpande VS, Kanters FMWW, Baaijens FPTT (2012) The influence of matrix integrity on stress-fiber remodeling in 3D. Biomaterials 33(30):7508–7518. https://doi.org/10.1016/j.biomaterials.2012.06.103 CrossRefGoogle Scholar
- Greaser ML, Gergely J (1971) Reconstitution of troponin activity from three protein components. J Biol Chem 246(13):4226–4233Google Scholar
- McMahon TA (1984) Muscles, reflexes, and locomotion. Princeton University Press, PrincetonGoogle Scholar
- Nieponice A, Maul TM, Cumer JM, Soletti L, Vorp DA (2007) ‘Mechanical stimulation induces morphological and phenotypic changes in bone marrow-derived progenitor cells within a three-dimensional fibrin matrix. J Biomed Mater Res, Part A 81A(3):523–530. https://doi.org/10.1002/jbm.a.31041 CrossRefGoogle Scholar
- Reynolds NH, Ronan W, Dowling EP, Owens P, McMeeking RM, McGarry JP (2014) On the role of the actin cytoskeleton and nucleus in the biomechanical response of spread cells. Biomaterials 35(13):4015–4025. https://doi.org/10.1016/j.biomaterials.2014.01.056 CrossRefGoogle Scholar