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In solid tumors, cells constantly interact with the surrounding extracellularmatrix. In particular cancer-associated fibroblasts modulate the architectureof the matrix by exerting forces and contracting collagen fibres, creatingpaths that facilitate cancer cell migration. The characterization of thecollagen fibre network and its space and time-dependent remodelling istherefore key to investigating the interactions between cells and the matrix,and to understanding tumor growth. The structural complexity and multiscalenature of the collagen network rule out classical image analysis algorithms,and call for specific methods. We propose an approach based on the mathematicalmodelling of the collagen network, and on the identification of the modelparameters from the correlation functions and histograms of grey-tone images.The specific model considered accounts for both the small-scale fibrillarstructure of the network and for the presence of large-scale aggregates. Whenapplied to time-resolved images of cancer-associated fibroblasts activelyinvading a collagen matrix, the method reveals two different densificationmechanisms for the matrix in direct contact or far from the cells. The veryobservation of two distinct phenomenologies hints at diverse mechanisms, whichpresumably involve both biochemical and mechanical effects.

Remodelling of the fibre-aggregate structure of collagen gels by  cancer-associated fibroblasts: a time-resolved grey-tone image analysis based  on stochastic modelling