Chemotropism among populations of yeast cells with spatiotemporal resolution in a biofabricated microfluidic platform.

Chemotropism is an essential response of organisms to external chemical gradients that direct the growth of cells toward the gradient source. Chemotropic responses between single cells have been studied using in vitro gradients of synthetically derived signaling molecules and helped to develop a better understanding of chemotropism in multiple organisms. However, dynamic changes including spatial changes to the gradient as well as fluctuations in levels of cell generated signaling molecules can result in the redirection of chemotropic responses, which can be difficult to model with synthetic peptides and single cells. An experimental system that brings together populations of cells to monitor the population-scale chemotropic responses yet retain single cell spatiotemporal resolution would be useful to further inform on models of chemotropism. Here, we describe a microfluidic platform that can measure the chemotropic response between populations of mating yeast A- and α-cells with spatiotemporal programmability and sensitivity by positioning cell populations side by side in calcium alginate hydrogels along semipermeable membranes with micrometer spatial control. The mating phenotypes of the yeast populations were clearly observed over hours. Three distinct responses were observed depending on the distance between the A- and α-cell populations: the cells either continued to divide, arrest, and develop a stereotypical polarized projection termed a "shmoo" toward the cells of opposite mating type or formed shmoos in random directions. The results from our studies of yeast mating suggest that the biofabricated microfluidic platform can be adopted to study population-scale, spatial-sensitive cell-cell signaling behaviors that would be challenging using conventional approaches.