The mechanisms by which organs acquire their functional structure and realize its maintenance (or homeostasis) over time are still largely unknown. In this paper, we investigate this question on adipose tissue. Adipose tissue can represent 20 to 50% of the body weight. Its investigation is key to overcome a large array of metabolic disorders that heavily strike populations worldwide. Adipose tissue consists of lobular clusters of adipocytes surrounded by an organized collagen fiber network. By supplying substrates needed for adipogenesis, vasculature was believed to induce the regroupment of adipocytes near capillary extremities. This paper shows that the emergence of these structures could be explained by simple mechanical interactions between the adipocytes and the collagen fibers. Our assumption is that the fiber network resists the pressure induced by the growing adipocytes and forces them to regroup into clusters. Reciprocally, cell clusters force the fibers to merge into a well-organized network. We validate this hypothesis by means of a two-dimensional Individual Based Model (IBM) of interacting adipocytes and extra-cellular-matrix fiber elements. The model produces structures that compare quantitatively well to the experimental observations. Our model seems to indicate that cell clusters could spontaneously emerge as a result of simple mechanical interactions between cells and fibers and surprisingly, vasculature is not directly needed for these structures to emerge.
We introduce an individual-based model for fiber elements having the ability to crosslink or unlink each other and to align with each other at the cross links. We first formally derive a kinetic model for the fiber and cross-links distribution functions. We then consider the fast linking/unlinking regime in which the model can be reduced to the fiber distribution function only and investigate its diffusion limit. The resulting macroscopic model consists of a system of nonlinear diffusion equations for the fiber density and mean orientation. In the case of a homogeneous fiber density, we show that the model is elliptic.
We provide a numerical study of the macroscopic model of Barré et al. (Multiscale Model Simul, 2017, to appear) derived from an agent-based model for a system of particles interacting through a dynamical network of links. Assuming that the network remodeling process is very fast, the macroscopic model takes the form of a single aggregation–diffusion equation for the density of particles. The theoretical study of the macroscopic model gives precise criteria for the phase transitions of the steady states, and in the one-dimensional case, we show numerically that the stationary solutions of the microscopic model undergo the same phase transitions and bifurcation types as the macroscopic model. In the two-dimensional case, we show that the numerical simulations of the macroscopic model are in excellent agreement with the predicted theoretical values. This study provides a partial validation of the formal derivation of the macroscopic model from a microscopic formulation and shows that the former is a consistent approximation of an underlying particle dynamics, making it a powerful tool for the modeling of dynamical networks at a large scale.
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