Collaborative Research: Multiscale Analysis and Simulation of Biofilm Mechanics

Yale University, New Haven CT

Investigators

Abstract

NON-TECHNICAL SUMMARY Once thought to live as solitary units, bacteria are now known to communicate with each other and live in lively microbial communities called biofilms. Biofilms can cause severe problems, including medical infections, fouling, and clogging in industrial applications. In contrast, biofilms play beneficial roles in wastewater treatment and microbial fuel cells. Scientists have been able to characterize the chemical components of biofilms but don’t know yet how an active, self-renewable, and self-healing material emerges from these components and their interactions. How can scientists use their vast knowledge of man-made polymers to understand these natural polymers? Are there new physical mechanisms to be discovered in the way bacteria build their biofilm communities? To answer these questions, this project aims to reveal the secrets of how biofilms derive mechanical properties from their individual components by integrating state-of-the-art mechanical measurement, single-cell imaging, and computer simulations. Through these fundamental studies, scientists can design better strategies that either eliminate harmful biofilms or use beneficial biofilms to create useful structures. By integrating multiple disciplines, this project will train a diverse group of students in the areas of biology, physics, materials science, and engineering, and prepare them for the next-generation workforce. The educational objectives of the project will be realized through curriculum development, undergraduate research opportunities, and K-12 outreach programs, with special efforts to involve underrepresented students. TECHNICAL SUMMARY Biofilms are surface-attached communities of bacteria embedded in a matrix made of extracellular polymeric substances (EPSs). The overarching goal of this project is to integrate state-of-the-art mechanical measurement, single-cell imaging, mutagenesis, computer simulations, and soft matter theory to address how, at different time and length scales, bacterial cells build communities with emerging mechanical properties. Specifically, the three research objectives are to (i) establish EPS as associative polymers crosslinked by matrix proteins, (ii) reveal the contribution of bacterial cells to biofilm mechanics, and (iii) measure the development of biofilm mechanics and heterogeneity at the single-cell level. These objectives are accomplished via experiments involving rheological testing, high-resolution imaging, protein biochemistry, bacterial genetics, and multiscale modeling. The broader impacts of this work are to help produce a diverse STEM-capable workforce by incorporating central concepts addressed in this project into education and outreach activities that expose and engage students in biology, materials science, physics, and engineering. The education and outreach activities center on the following three objectives: (i) expanding the Pathways to Science program for local high school students, (ii) incorporating research findings into the curriculum for both undergraduate and graduate courses, and (iii) providing research experiences to underrepresented minority students. 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.