Speaker
Description
In this talk, we investigate how organs acquire functional structure and rebuild after injury using Individual Based Models (IBM) confronted with experimental data. We first study simple 2D and 3D models for architecture emergence, with cells appearing and growing in a dynamic network of cross-linked fibers. Cells and fibers interact via mechanical repulsion. When applied to adipose tissue, the model reproduces experimental structures and suggests that cell clusters could spontaneously emerge from simple cell–fiber interactions. By implying that vasculature could be secondary to tissue architecture, this simple model therefore proposes a new view of tissue development. In the second part of the talk, we extend the model to account for tissue repair, exploring mechanisms of adipose tissue regeneration. The model successfully generates regeneration or scar formation as functions of few key parameters and indicates that injury outcomes largely depend on ECM rigidity. Via a combined in vivo/in silico approach, the model enables to identify a therapeutically validated target enabling regeneration in mouse adipose tissue. Altogether, these studies point to the essential role of mechanics in tissue structuring and regeneration, and bring a comprehensive view on the role of ECM crosslinking on tissue architecture emergence and reconstruction.
