10779/crick.11638029.v1 Esther Wershof Esther Wershof Danielle Park Danielle Park Robert P Jenkins Robert P Jenkins David J Barry David J Barry Erik Sahai Erik Sahai Paul A Bates Paul A Bates Matrix feedback enables diverse higher-order patterning of the extracellular matrix. The Francis Crick Institute 2020 Bates FC001003 Sahai FC001144 LM CB-ack 06 Biological Sciences 08 Information and Computing Sciences 01 Mathematical Sciences Bioinformatics 2020-01-17 16:57:21 Journal contribution https://crick.figshare.com/articles/journal_contribution/Matrix_feedback_enables_diverse_higher-order_patterning_of_the_extracellular_matrix_/11638029 The higher-order patterning of extra-cellular matrix in normal and pathological tissues has profound consequences on tissue function. Whilst studies have documented both how fibroblasts create and maintain individual matrix fibers and how cell migration is altered by the fibers they interact with, a model unifying these two aspects of tissue organization is lacking. Here we use computational modelling to understand the effect of this interconnectivity between fibroblasts and matrix at the mesoscale level. We created a unique adaptation to the Vicsek flocking model to include feedback from a second layer representing the matrix, and use experimentation to parameterize our model and validate model-driven hypotheses. Our two-layer model demonstrates that feedback between fibroblasts and matrix increases matrix diversity creating higher-order patterns. The model can quantitatively recapitulate matrix patterns of tissues in vivo. Cells follow matrix fibers irrespective of when the matrix fibers were deposited, resulting in feedback with the matrix acting as temporal 'memory' to collective behaviour, which creates diversity in topology. We also establish conditions under which matrix can be remodelled from one pattern to another. Our model elucidates how simple rules defining fibroblast-matrix interactions are sufficient to generate complex tissue patterns.