Multiscale biphasic modelling of peritumoural collagen microstructure: The effect of tumour growth on permeability and fluid flow.

We present an in-silico model of avascular poroelastic tumour growth coupled with a multiscale biphasic description of the tumour-host environment. The model is specified to in-vitro data, facilitating biophysically realistic simulations of tumour spheroid growth into a dense collagen hydrogel. We use the model to first confirm that passive mechanical remodelling of collagen fibres at the tumour boundary is driven by solid stress, and not fluid pressure. The model is then used to demonstrate the influence of collagen microstructure on peritumoural permeability and interstitial fluid flow. Our model suggests that at the tumour periphery, remodelling causes the peritumoural stroma to become more permeable in the circumferential than radial direction, and the interstitial fluid velocity is found to be dependent on initial collagen alignment. Finally we show that solid stresses are negatively correlated with peritumoural permeability, and positively correlated with interstitial fluid velocity. These results point to a heterogeneous, microstructure-dependent force environment at the tumour-peritumoural stroma interface.