A Mathematical Modelling Framework to Investigate the Alignment of Fibroblasts

A Mathematical Modelling Framework to Investigate the Alignment of Fibroblasts #

Vivienne Leech

14:50 Monday in 3Q68.

Part of the Cell and tissue mechanics session.

Abstract #

Fibroblasts are cells that help to maintain the structural framework of tissue, and are of interest when looking at fibrotic tissue. In this work we hope to better understand the mechanisms behind the long range alignment of fibroblasts in keloid scar tissue, as a pathway to better understanding the causes of tissue fibrosis. Keloid fibroblasts have been observed to align with each other over a longer length-scale and shorter time-scale compared to normal fibroblasts, but the mechanism behind this long range alignment is unclear. Models so far have explored the nature of this alignment, but not whether the alignment can arise purely from force based interactions. We start by deriving and simulating a simplified agent based model that incorporates physical, force based interactions between cells to see whether this is enough to account for the long range alignment that is observed experimentally. Simulations can be compared with experimental data to assess the validity of the model. We find that while this leads to some alignment, it is not enough alignment to account for what we observe experimentally. The model is then extended accordingly, incorporating further mechanisms such as force transmission through cell-cell junctions and dynamic cell shapes. We explore how these extra mechanisms affect the alignment, allowing us to obtain a better understanding of what the experimental mechanism could be.