Modeling cell populations metabolism and competition under maximum power constraints.

Conte, Luigi; Gonella, Francesco; Giansanti, Andrea; Kleidon, Axel; Romano, Alessandra

Ecological interactions are fundamental at the cellular scale, addressing the possibility of a description of cellular systems that uses language and principles of ecology. In this work, we use a minimal ecological approach that encompasses growth, adaptation and survival of cell populations to model cell metabolisms and competition under energetic constraints. As a proof-of-concept, we apply this general formulation to study the dynamics of the onset of a specific blood cancer—called Multiple Myeloma. We show that a minimal model describing antagonist cell populations competing for limited resources, as regulated by microenvironmental factors and internal cellular structures, reproduces patterns of Multiple Myeloma evolution, due to the uncontrolled proliferation of cancerous plasma cells within the bone marrow. The model is characterized by a class of regime shifts to more dissipative states for selectively advantaged malignant plasma cells, reflecting a breakdown of self-regulation in the bone marrow. The transition times obtained from the simulations range from years to decades consistently with clinical observations of survival times of patients. This irreversible dynamical behavior represents a possible description of the incurable nature of myelomas based on the ecological interactions between plasma cells and the microenvironment, embedded in a larger complex system. The use of ATP equivalent energy units in defining stocks and flows is a key to constructing an ecological model which reproduces the onset of myelomas as transitions between states of a system which reflects the energetics of plasma cells. This work provides a basis to construct more complex models representing myelomas, which can be compared with model ecosystems. Author summary: Ecological interactions at the scale of cell populations are important to understand the emergent behavior of complex biological systems as diseases. Despite the extensive knowledge of the molecular and cellular details of biomedical systems, understanding the mechanisms behind the onset of Multiple Myeloma and predicting its dynamic evolution is a challenge. For diseases characterized by recurrent patterns and non-genetic plasticity, it is not possible to eradicate the mechanism that sustains cancer onset and evolution, namely they are defined as incurable. This mechanism is not typical of blood cancer itself, being a general emergent behavior of ecological systems as determined by the complex interactions between system's elements and the environment. Unfolding the role of the competitive interaction between normal, cancerous cell populations and the micro-environment by quantifying the energetic constraints operating on them is of key relevance. Here, adopting an energetic approach, we show that it is possible to reproduce stylized patterns of Multiple Myeloma onset by means of a minimal stock-flow ecological model of competing normal and malignant plasma cell populations. Our results suggest the potential of this general approach to build more detailed models of Multiple Myeloma, as well as to study biological systems and diseases.

CELL populations; B cells; CELL metabolism; BIOLOGICAL systems; CELL anatomy; BONE marrow cells

PLoS Computational Biology, 2023, Vol 19, Issue 11, p1

1553-734X

Academic Journal

10.1371/journal.pcbi.1011607