The Biophysical Foundations of Bacterial Biofilm Growth and Survival - Bacteria play important roles in human health, acting as pathogens and members of healthy microbiomes. Though the classic picture of bacteria is that of solitary cells in planktonic suspension, a growing body of evidence suggests that the primary state of bacteria is the biofilm: surface-attached, crowded communities of microbes and extracellular matrix. Further, the importance of biofilms has been demonstrated in ecology and human health. Thus, biofilm formation represents a fundamental aspect of bacterial physiology. It may seem that biofilm growth could be understood by extrapolating from the growth of individual cells – simply by examining how single cells grow and scale by the total number of bacteria. However, when cells form a biofilm, they create a physical structure with biological, chemical, and physical properties beyond those that individual cells can achieve. Microbes in biofilms are mechanically, topologically, geometrically, and functionally constrained by physical interactions between themselves and with their environment. These physical interactions also create opportunities; by being physically together bacteria can accomplish more than what they can alone, from creating mechanically robust structures, to efficiently using secreted public goods. Further, microbes often alter their gene expression in response to these physical challenges and opportunities, creating a biophysical-behavioral feedback loop. Thus, the growth of biofilms as complex, multicellular structures is an intrinsically emergent phenomenon that cannot be understood from studying isolated cells. To understand biofilms, we therefore must focus not only on cellular biology, but on multicellular biology. We aim to understand how biofilms become more than clumps of cells to produce novel multicellular structures, functions, and behaviors. First, we will examine biofilm development in complex environments, exploring how the underlying biophysics is affected as we move away from simple environments. Complementing these experiments, we will study the biophysical growth dynamics of polyclonal biofilms, which more closely reflect the diversity found in natural microbial communities. We will also explore the biophysics underlying biofilm survival, with a focus on the impacts of starvation, desiccation, and feast-famine cycles—phenomena that affect survival in most natural environments but are less studied in the lab. Starvation and feast-famine cycles are relevant in nearly every environment outside the lab; desiccation is relevant for air-solid interface biofilms, such as those in the built environment, or in environments in which water levels change (e.g., receding flood waters, droughts, etc.). Alongside these experimental studies, we will work to further improve our biophysical models of biofilm growth to these unique scenarios, creating more accurate and predictive simulations of biofilm behavior. By studying these phenomena, we will generate a more thorough understanding of the biophysical mechanisms underlying biofilm growth. The knowledge gained is of fundamental biofilm physiological importance, with broad implications for fields ranging from medicine to engineering to environmental science.
