A modeling study of budding yeast colony formation and its relationship to budding pattern and aging

Abstract

Budding yeast, which undergoes polarized growth during budding and mating, has been a useful model system to study cell polarization. Bud sites are selected differently in haploid and diploid yeast cells: haploid cells bud in an axial manner, while diploid cells bud in a bipolar manner. While previous studies have been focused on the molecular details of the bud site selection and polarity establishment, not much is known about how different budding patterns give rise to different functions at the population level. In this paper, we develop a two-dimensional agent-based model to study budding yeast colonies with cell-type specific biological processes, such as budding, mating, mating type switch, consumption of nutrients, and cell death. The model demonstrates that the axial budding pattern enhances mating probability at an early stage and the bipolar budding pattern improves colony development under nutrient limitation. Our results suggest that the frequency of mating type switch might control the trade-off between diploidization and inbreeding. The effect of cellular aging is also studied through our model. Based on the simulations, colonies initiated by an aged haploid cell show declined mating probability at an early stage and recover as the rejuvenated offsprings become the majority. Colonies initiated with aged diploid cells do not show disadvantage in colony expansion possibly due to the fact that young cells contribute the most to colony expansion.

Multi-Scale Mathematical Modeling of Prion Aggregate Dynamics and Phenotypes in Yeast Colonies

“…Developing a modeling framework for investigating prion disease dynamics within an entire yeast colony is challenging because it requires capturing the physical processes on an individual cell level that determine colony growth (i.e., budding and variable cell cycle length) as well as capturing the interplay of individual cell processes with protein aggregation dynamics (i.e., asymmetric protein distribution at the time of division, persistence of diseased phenotype/aggregate that was given to daughter while it grows to begin a new cell cycle, lineage-dependent protein propagation). Several models have already been developed to investigate physical mechanisms controlling patterns of yeast colony growth such as cell division polarity, mother-daughter size asymmetry, and cell-cell adhesion via budding of the new daughter cell [92,93,105]. Jönsson and Levchenko developed an offlattice, center-based model in which cells are modeled as elastic spheres of variable size [92].…”

“…Their work showed that cell growth inhibition by neighboring cells and polar division growth patterns were the most significant factors driving appreciable differences in the shape and size of yeast colony development. In addition, Wang et al built an off-lattice, center-based model that incorporates key biological processes in yeast cell colonies including budding, mating, mating type switch, changes in cell cycle length and cell size due to aging, and cell death [93]. The main results of their work include proposed mechanisms for how budding patterns in yeast cells affect colony growth.…”

“…Lattice-free modeling approaches vary in complexity from those that track the center of each cell as a single point [91][92][93] to those that represent individual cells as collections of membrane and cytoplasm nodes to allow for more biologically relevant, emerging cell shapes [89,94,95]. Although a main advantage of CA methods has been their computational efficiency, as computational power continues to increase, lattice-free modeling approaches offer equally powerful tools for realistically modeling biological cell behaviors such as shape change, polarized cell growth, division, differentiation, and intercellular signaling dynamics in great detail without adding computational complexity.…”

“…Center-based models have been used to analyze multicellular processes in tumors [91,99,100], intestinal crypts and epithelial tissues [85,103], cell migration in extracellular matrix [85,100], and tissue regeneration, growth, and organization [91,99,100,103,104]. In addition, several center-based models have been developed for studying macroscopic properties of yeast colonies [92,93,105]. (See Section 4 for more details.)…”

A Role for Cell Polarity in Lifespan and Mitochondrial Quality Control in the Budding Yeast Saccharomyces cerevisiae

“…Bud1p/Rsr1p, a Rho-GTPase family protein, is a core component of the cell polarity machinery that is essential for polarized bud site selection in yeast. Polarized bud site selection may promote colony expansion in diploid yeast or mating in haploid yeast (Wang et al, 2017).…”