Simple mechanical cues could explain adipose tissue morphology

Abstract

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.

Kinetic Theory of Particle Interactions Mediated by Dynamical Networks

“…A good biological example for this kind of assumption would be the process of growth of adipose tissue studied in [26]. It takes about 100 days for a nascent adipocyte to grow to its maximum size, while for the extracellular matrix complete remodeling takes up to 15 days.…”

“…Nevertheless, one common feature of these systems is the strong coupling between the dynamical evolution of the individual agents (cells or monomers, for instance) with that of the network mediating their interactions. The mathematical modeling of this strongly coupled dynamics is a challenging task (see, for example, [26]) but it is a necessary step toward building more complete models of complex biological or social phenomena.…”

Extra-cellular matrix rigidity may dictate the fate of injury outcome

“…(i) Introduction of new fibers/cells. To create a simulation framework that addresses the mechanical features of adipogenesis and homeostasis, a 2D individual based model (IBM) was introduced in [46]. Here, we use the same framework to model tissue repair after injury.…”

“…The choice of fiber length and width is motivated by studies of [57], where it is shown that the collagen fibers are organized into bundles of collagen fibrils the width of which varying from 1 to 20µm depending on tissues and organs. In order to enable the fibers to bend around the cells, the fiber elements are chosen to be 20µm wide and 60µm long (the adipocyte diameter being 60µm, see [46]). The model parameters used for the simulations are given in table 1.…”

“…The model developed in this paper is based on an existing model [46] which we modify to take into consideration the previously described phases of tissue repair. In section 2., we will first present the main ingredients of the model and motivate the choice of the model parameter values with biological measurements (section 2).…”