Abstract
Microbial colonies are fascinating structures in which growth and internal organization reflect complex morphogenetic processes. Here, we generated a microfluidics device with arrays of long monolayer yeast colonies to further global understanding of how intercellular metabolic interactions affect the internal structure of colonies within defined boundary conditions. We observed the emergence of stable glucose gradients using fluorescently labeled hexose transporters and quantified the spatial correlations with intra-colony growth rates and expression of other genes regulated by glucose availability. These landscapes depended on the external glucose concentration as well as secondary gradients, for example amino acid availability. This work demonstrates the regulatory genetic networks governing cellular physiological adaptation are the key to internal structuration of cellular assemblies. This approach could be used in the future to decipher the interplay between long-range metabolic interactions, cellular development and morphogenesis in more complex systems.
Highlights
Structured cellular populations are complex, dynamic systems and their composition, expansion and internal structure are the result of interactions between the cells and their microenvironment
In attempt to overcome the above limitations in current methodologies and observe emerging properties at a colony level in larger dimensions and standard nutrient conditions, we developed a microfluidic device to grow thin, extended arrays of yeast cell monolayers that are perfused with nutrients from a single direction
We demonstrate the emergence of heterogeneous microenvironments and quantify spatial variation in cellular growth rate and the formation of gene expression landscapes for key metabolic genes involved in glucose transport and utilization, across the nascent 2D microcolony in 800 mm long cell chambers and up to 444 mM glucose concentration
Summary
Structured cellular populations are complex, dynamic systems and their composition, expansion and internal structure are the result of interactions between the cells and their microenvironment. Such variations in cellular physiology are consistently observed in a variety of multicellular systems – from bacterial and yeast colonies (Vulin et al, 2014; Cap et al, 2012) to biofilms (Nadell et al, 2016) and tumors (CarmonaFontaine et al, 2013; Delarue et al, 2014) – and are reflected by altered gene expression levels and cellular phenotypes as growth rates, nutrient uptake rates and metabolic activity Such variations presumably emerge because of long-range metabolic interactions between cells, in that the cellular microenvironment at one position depends on the nutrient uptake rate at another position
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