ENERgy driven modelling of tissue architecture emerGENCE and homeorhesis – ENERGENCE

With the increase in life expectancy in most countries, understanding the mechanisms of tissue decline has become a major public health priority for our society. Decline of tissue functions is correlated with a loss of its architecture. The emergence of this architecture and subsequent maintenance and decline involves energy exchanges and mechanical forces, and perturbation of one or the other is associated to degeneration and diseases. Therefore, understanding the dynamics of biological tissues requires to account simultaneously for energy exchanges and mechanical considerations, a view that is currently lacking. The goal of ENERGENCE is to fill this gap by developing a complete theoretical and experimental framework that enables to decipher the complex interplay between metabolism and mechanics. We propose that different stages of tissue evolution are akin to different phases of a complex social systems driven by few key determinants, interacting together mechanically and constantly exchanging energy with their environment. We will focus on adipose tissue as a biological model because its architecture is relatively simple and largely dependent on energy exchanges, and as a target with the world-wide development of the obesity epidemic. The methodology relies on a synthetic approach based on a dual use of mathematical modelling and in-vitro/in-vivo experiments. We will develop agent-based models (ABM) to test the modelling hypotheses and derive continuous models from the ABM to explore theoretically and numerically long-term large-scale effects. All theoretical models will be validated with biological experiments on different mice using state-of-the-art model calibration and model-data coupling methodologies. This approach will enable to decipher the key factors involved in the evolution of tissue architecture at different spatio-temporal scales. This new understanding of aging will pave the way for new therapies related to metabolic and degenerative diseases.