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.