Existence and stability of periodic solutions of an impulsive differential equation and application to CD8 T-cell differentiation

TL;DR

This paper models molecular partitioning during cell division using impulsive differential equations, analyzing the existence and stability of periodic solutions, and applies these findings to understand CD8 T-cell differentiation and heterogeneity.

Contribution

It introduces a novel impulsive differential equation model for cell division and provides a comprehensive analysis of periodic solutions and their stability, with applications to T-cell differentiation.

Findings

Partitioning asymmetry influences cell fate decisions.

Periodic solutions depend on the impulse timing and magnitude.

Molecular heterogeneity affects immune cell differentiation.

Abstract

Unequal partitioning of the molecular content at cell division has been shown to be a source of heterogeneity in a cell population. We propose to model this phenomenon with the help of a scalar, nonlinear impulsive differential equation (IDE). In a first part, we consider a general autonomous IDE with fixed times of impulse and a specific form of impulse function. We establish properties of the solutions of that equation, most of them obtained under the hypothesis that impulses occur periodically. In particular, we show how to investigate the existence of periodic solutions and their stability by studying the flow of an autonomous differential equation. A second part is dedicated to the analysis of the convexity of this flow. Finally, we apply those results to an IDE describing the concentration of the protein Tbet in a CD8 T-cell, where impulses are associated to cell division, to study the effect of molecular partitioning at cell division on the effector/memory cell-fate decision in a CD8 T-cell lineage. We show that the degree of asymmetry in the molecular partitioning can affect the process of cell differentiation and the phenotypical heterogeneity of a cell population.