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Multiscale modelling of solid tumour growth: the effect of collagen micromechanics

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Abstract

Here we introduce a model of solid tumour growth coupled with a multiscale biomechanical description of the tumour microenvironment, which facilitates the explicit simulation of fibre–fibre and tumour–fibre interactions. We hypothesise that such a model, which provides a purely mechanical description of tumour–host interactions, can be used to explain experimental observations of the effect of collagen micromechanics on solid tumour growth. The model was specified to mouse tumour data, and numerical simulations were performed. The multiscale model produced lower stresses than an equivalent continuum-like approach, due to a more realistic remodelling of the collagen microstructure. Furthermore, solid tumour growth was found to cause a passive mechanical realignment of fibres at the tumour boundary from a random to a circumferential orientation. This is in accordance with experimental observations, thus demonstrating that such a response can be explained as purely mechanical. Finally, peritumoural fibre network anisotropy was found to produce anisotropic tumour morphology. The dependency of tumour morphology on the peritumoural microstructure was reduced by adding a load-bearing non-collagenous component to the fibre network constitutive equation.

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Notes

  1. FEB3: Finite Element Bioengineering in 3D, publicly available from https://bitbucket.org/vasvav/feb3-finite-element-bioengineering-in-3d.

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Acknowledgments

The authors from UCL would like to thank Dr. Rebecca Shipley (UCL IBME) for many useful discussions. The authors from UCL received funding from EPSRC grant “MIMIC”: EP/K020439/1, EU FP7 Virtual Physiological Human grant: “VPH-PRISM” (FP7-ICT-2011-9, 601040) and Marie-Curie Fellowship (FP7-PEOPLE-2013-IEF, 627025). The authors from UCY received funding from the European Research Council (FP7/2007-2013)/ERC Grant No. 336839-ReEngineeringCancer.

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Authors and Affiliations

  1. Department of Medical Physics and Bioengineering, Centre for Medical Image Computing, University College London, Engineering Front Building, Malet Place, London, WC1E 6BT, UK

    Peter A. Wijeratne, Vasileios Vavourakis, John H. Hipwell & David J. Hawkes

  2. Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678, Nicosia, Cyprus

    Chrysovalantis Voutouri, Panagiotis Papageorgis & Triantafyllos Stylianopoulos

  3. Ninewells Medical School, Dundee, DD1 9SY, UK

    Andrew Evans

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  1. Peter A. Wijeratne
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  2. Vasileios Vavourakis
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Correspondence to Peter A. Wijeratne.

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Wijeratne, P.A., Vavourakis, V., Hipwell, J.H. et al. Multiscale modelling of solid tumour growth: the effect of collagen micromechanics. Biomech Model Mechanobiol 15, 1079–1090 (2016). https://doi.org/10.1007/s10237-015-0745-2

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