title: Multiscale modelling of solid tumour growth: the effect of collagen micromechanics.
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.
authors.affiliation: Department of Medical Physics and Bioengineering, Centre for Medical Image Computing, University College London, Engineering Front Building, Malet Place, London, WC1E 6BT, UK. p.wijeratne@ucl.ac.uk.
authors.forename: Peter A
authors.identifier: 0000-0002-4885-6241
authors.initials: PA
authors.lastname: Wijeratne
authors.affiliation: Department of Medical Physics and Bioengineering, Centre for Medical Image Computing, University College London, Engineering Front Building, Malet Place, London, WC1E 6BT, UK.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Vavourakis
authors.affiliation: Department of Medical Physics and Bioengineering, Centre for Medical Image Computing, University College London, Engineering Front Building, Malet Place, London, WC1E 6BT, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Hipwell
authors.affiliation: Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678, Nicosia, Cyprus.
authors.forename: Chrysovalantis
authors.initials: C
authors.lastname: Voutouri
authors.affiliation: Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678, Nicosia, Cyprus.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papageorgis
authors.affiliation: Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678, Nicosia, Cyprus.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Stylianopoulos
authors.affiliation: Ninewells Medical School, Dundee, DD1 9SY, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.affiliation: Department of Medical Physics and Bioengineering, Centre for Medical Image Computing, University College London, Engineering Front Building, Malet Place, London, WC1E 6BT, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hawkes
mesh_terms: D000465:Algorithms; D000818:Animals; D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism*; D003198:Computer Simulation; D020342:Finite Element Analysis; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013314:Stress, Mechanical; D047368:Tumor Burden
chemical_list: D003094:Collagen
keywords: Fibre remodelling; Finite element analysis; Microenvironment; Tumour mechanics