Biofilms are communities of microbes that are bound to each other by a matrix of polymers and proteins that they produce in which to live. Biofilms foul and corrode pipes, and partially cause chronic infections in animals and humans. The biofilm "hides" the bacteria from many antibiotics and bacteriocides, and also masks them from the immune system. This project is to determine the role of shear mechanics in the creating the biofilms made by an important pathogen that affects humans. This will benefit society by laying the groundwork for new approaches to preventing and clearing biofilms that target mechanical characteristics. Today the approaches to preventing biofilms focus, with limited success, on developing surfaces that resist bacterial attachment or that kill bacteria. Mature biofilms often resist treatment, except by mechanical removal, and mechanical breakup of biofilms can also increase vulnerability to conventional antibiotics. Almost nothing is known about how different matrix materials control the mechanics of biofilms. This research will improve biofilm prevention and remediation and benefit public health and infrastructure where biofilms are a problem such as in the piping of water treatment plants, and oil transport piping. Educational modules to be developed in the first Educational goal will be aligned with standards for high school curricula in biology, physics, and math, provide an experiential understanding of how scientific knowledge is developed and teach discipline-crossing core concepts. The second educational goal will lead to better strategies for improving the long-term undergraduate STEM pipeline for both traditional and under-represented groups.
Pseudomonas aeruginosa is a model organism with well-characterized genetics and molecular biology, and also readily forms biofilms with important industrial and medical impact. Biofilm mechanics will be measured using rheology. Controlled stress will be applied to single bacteria and to bacteria within biofilms, and the resulting signaling, phenotypic changes, and biofilm development will be measured. Genetic manipulation will be used to elucidate how specific gene products contribute to specific mechanical properties and to mechanosensing, signaling, and biofilm initiation. Research Aims are: (1) determine the role of shear mechanics in triggering the signal that initiates biofilm development - this will reveal design principles for surfaces that thwart mechanosensing and thereby prevent biofilm initiation; (2) determine the role of specific biofilm components in contributing to mechanical resilience of the mature biofilm - this will result in strategies for disruption and clearance that are tunable to specific matrix composition and mechanical properties; (3) determine the mechanosensory response of constituent bacteria to biofilm stiffness and strain - this will indicate how to reduce biofilms' ability to dynamically adapt and increase their mechanical robustness. (1) Research Aim 1 will result in a new paradigm for biofilm prevention that targets highly-conserved signaling mechanisms for which evolutionary escape will be difficult or impossible. (2) Research Aim 2 will result in a new framework for understanding the mechanics of biofilms as composites. (3) Research Aim 3 will result in new knowledge of how biofilms may act as multicellular, force sensitive "tissues".
