Weyer, H. | bioRxiv Science

bioRxiv2024

Basic interactions responsible for thymus function explain convoluted medulla shape

The thymus is one of the most important organs of the immune system. It is responsible for both the production of T cells and the prevention of their autoimmunity. It comprises two types of tissue: the cortex, where nascent T cells (thymocytes) are generated; and the medulla, embedded within the cortex, where autoreactive thymocytes are eliminated through negative selection. In mice, the medulla exhibits a complex, convoluted morphology, which has raised the question of whether its form impacts its function. Intriguingly, experiments also reveal a reverse dependency: the interactions between medullary stroma and thymocytes shape the medullary structure. However, understanding the underlying mechanisms of medulla morphogenesis emerging from these interactions remains elusive. Here, we present a conceptual theoretical model which shows that central, experimentally verified signaling pathways suffice to shape the convoluted medullary structure. The mathematical analysis of the model explains the observed effects of chemotaxis on thymocyte localization, as well as the reported morphological changes resulting from the modulation of thymocyte production. Our findings reveal that the established cross-talk between medulla growth and negative selection of thymocytes not only regulates medullary volume but also orchestrates the morphology of the thymus medulla. This mechanism of structure formation robustly organizes the medulla in a way that accelerates thymocyte negative selection by improving their chemotactic migration into the medulla. Thereby, we identify a feedback between the function of the thymus medulla and its form. Our theoretical study motivates further experimental analysis of the spatial distribution of thymic cell populations and predicts morphological changes under genetic perturbations.

biophysics↗

bioRxiv2023

Robust and resource-optimal dynamic pattern formation of Min proteins in vivo

The Min system in Escherichia coli plays a crucial role in cellular reproduction by preventing minicell formation through pole-to-pole oscillations. Despite extensive research, predicting the onset of Min protein concentrations for oscillation and understanding the systems robustness under physiological perturbations remains challenging. Our study aims to address these gaps. We show that the Min systems dynamic pattern formation is robust across a wide range of Min protein levels and varying growth physiology. Using genetically engineered E. coli strains, we independently modulated the expression of minCD and minE in E. coli under both fast and slow growth conditions. This led to the construction of a MinD-MinE phase diagram, which revealed not just a large oscillation regime but also complex dynamic patterns such as traveling and standing waves. Interestingly, we found that the natural expression level of Min proteins is nearly optimal. Our work combines experimental findings with biophysical theory based on reaction-diffusion models, reproducing the experimental phase diagram and other key properties quantitatively. This includes the observation of an invariant wavelength of dynamic Min patterns across our phase diagram. Crucially, the success of our model depends on the switching of MinE between its latent and active states, indicating its essential role as a robustness module for Min oscillation in vivo. Our results underline the potential of integrating quantitative cell physiology and biophysical modeling in understanding the fundamental mechanisms controlling cell division machinery, offering insights applicable to other biological processes.

biophysics↗