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We propose a 2D individual-based model for cells interacting in a complex interconnected fiber network, based on the hypothesis that adipose tissue morphogenesis could be principally driven by mechanical cues between the adipocytes and the Extra-Cellular Matrix, and that vascularization could be secondary to this organisation.
Left: Microscopy image of mature adipose tissue from an adult mice. Right: Simulation of the 2D agent-based model
Quantitative comparison between microscopy images (left) and simulations (right)
Collaborations:
L. Casteilla, A. Lorsignol, C. Barreau (StromaLab,Toulouse), P. Degond (Imperial College London), J. Rouquettes (ITAV ,Toulouse), F. Delebecque (IMT, Toulouse), X. Descombes (INRIA Nice Sophia Antipolis)
Project publications:
D. Peurichard, F. Delebecque, A. Lorsignol, C. Barreau, J. Rouquette , X. Descombes, L. Casteilla and P. Degond, Simple mechanical cues could explain adipose tissue morphology, Journal of Theoretical Biology (2017). https://doi.org/10.1016/j.jtbi.2017.06.030, lien arXiv
Numerical simulations
Numerical simulations
Model ingredients:
Adipocytes are modeled as 2D spheres and fibers as segments of fixed length. Biological phenomena include (i) formation/breakage of crossing fibers dynamically in time, (ii) cell growth, (iii) stem cell differentiation. Mechanical interactions include (i) cross-linked fiber alignment (ii) cell-fiber and fiber-fiber repulsion, (iii) cell-cell non overlapping (iv) fiber-fiber maintain of the links.
We show some simulations that highlight the importance of the ECM mechanical properties in the geometry of the cell and fiber structures at equilibrium.
Legend: Agents : Red : cells (2D spheres), blue: fibres (straight lines), green: fiber links.
1. Moderatedly stiff networks, fixed number of links: In a moderatly stiff fiber network, cells and fibers self-organize to form lobule-like structures of cells in a stiff fiber network (moderately organized). Biologically relevant cell and fiber structures are obtained, with a fiber network slightly more disorganized than in real tissues.
S1_Video.avi2. Highly constrained fiber networks (high number of fiber links): In a very constrained fiber network, cells are subject to large mechanical constraints that compress the whole cellular structure, the fiber network is disorganized because of the large number of fixed fiber links. The obtained fiber network could represent a pathological situation such as fibrosis.
S2_Video.aviLink: https://doi.org/10.6084/m9.figshare.4004697
3. Moderately dynamical fiber network, moderate number of links: Cells and fibers self-organize to form lobule-like structures of cells in an organized fiber network. The dynamical linking/unlinking favors the organization of the fiber network compared to a fixed number of fiber links (to be compared with S1 Video). Biologically relevant cell and fiber structures are obtained.
4. Highly dynamical fiber networks, large number of links: By reorganizing fast, the fiber network aligns rapidly, transferring its alignment to the surrounding cell structures
S3_Video.aviLink: https://doi.org/10.6084/m9.figshare.4004697
S2_Video.aviLink: https://doi.org/10.6084/m9.figshare.4004697
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