Multiscale Studies of Collective Behavior in a Model Social Bacterium

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The ability of groups of individuals to form complex and dynamic spatial patterns is a key aspect of biological phenomena ranging from collective behavior to multi-cellularity to development. In a cellular context, this often involves complicated chemical signaling and chemotaxis strategies. However, the PI has recently discovered that some bacterial species have evolved to take advantage of an active-matter phase separation that generates patterns without the need for chemical signaling. This project strives to understand this process from a physicist's perspective, but is hindered by a lack of tools to physically probe the mechanical properties and interactions of groups of motile bacteria. The PI's work with the single-celled bacterium Myxococcus xanthus focuses on the molecular details of force generation and the interactions of cells at the start of collective starvation-induced fruiting body formation. In this project, the PI seeks to explain the process of fruiting body development as an active dewetting process, linking new theoretical models with cutting-edge experimental data. The PI's research goals are complemented by an outreach plan that aims to involve more undergraduate students in biological physics and to engage non-scientists through public lectures. The PI's goals over the next few years include (i) expanding the Integrated Science program for first year undergraduates, (ii) starting a summer school aimed at advanced undergraduates, and (iii) putting on a series of public lectures in New York City meant to convey the excitement and innovation of biophysics using examples relevant to everyday life.The three aims below seek to determine the role of motility and adhesion in driving starvation-based dewetting. The PI's current models of Myxococcus xanthus aggregation rely on particle jamming in 2D. While these incredibly simple models capture some of the observed phenomena, the actual dynamics occur in 3D as the population dewets off the surface without jamming to form round droplets. This more complicated reality requires more sophisticated experimental data. The laboratory combines expertise in Myxococcus xanthus motility, cutting-edge imaging techniques, force microscopy, and computer vision analyses, making the group uniquely qualified to carry out the proposed research. Aim 1: To understand the forces that cells generate on each other and on a substrate, the PI will measure cell-cell and cell-substrate mechanical interactions using a custom-built optical trapping microscope and mutant strains that lack specific motor proteins and adhesion molecules. Aim 2: To probe the motility of cells inside a fruiting body, the group will track cells in 3D using confocal microscopy to (i) compare the motion over time and between different locations in the aggregate, and (ii) investigate the formation of layered structures and flows within the fruiting body. Aim 3: To probe the macroscopic mechanics involved in fruiting body formation, the group will (i) measure the development of droplet shape and rheology using confocal imaging and atomic force microscopy, and (ii) probe the forces generated on the substrate using traction force microscopy. At each step, data from the three aims will be used to test, and be tested by, the active-dewetting theories being developed by the group's collaborators. This project lies firmly within the goals of the Physics of Living Systems program at the NSF by using physical measurements and analyses to understand the dynamics of living cells across spatial scales.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.