Human Frontiers Science Program (HFSP) Center for Early Biofilm Development

Bacterial biofilms are integrated communities of cells that adhere to surfaces and are fundamental to the ecology and biology of bacteria. The accommodation of a free-swimming cell to a solid surface is more complex than passive cell adhesion. Our
HFSP Center uses a multi-disciplinary approach to investigate the interplay between motility appendages, molecular motors, exopolysaccharide (EPS) production, and hydrodynamics near the surface environment using tools not usually used by bacteriologists. We address two questions in P. aeruginosa.

How do different bacterial motor systems and EPS interact with solid surfaces? How do flagella/TFP adapt and respond to an interaction with a surface, and how do they couple to near-surface hydrodynamics and EPS? We examine the transition from swimming to attaching for the two principal motor systems, flagella and type IV pili (TFP), using direct force measurements on single motors and correlate with multicell behavior using single cell tracking techniques. In all cases, the different roles of solid versus viscous friction in this low Reynolds number regime can significantly impact behavior. With these anchoring measurements it will be possible to examine this important cdiGMP signaling network in a new light.

How do bacterial motors, exopolysaccharides, and guiding signals influence early biofilm formation? We track the entire motility history of every cell and make inferences about biofilm initiation at single cell resolution.  Single molecule TFP force measurements are used to examine the possibility of TFP and flagella sensing functions for EPS and EPS-mediated interactions between cells. Results are interpreted using theoretical techniques developed to study nonlinear feedback mechanisms and stochastic models. Our physical measurements are combined with techniques to measure cdiGMP levels at the single cell level, so that spatiotemporal phenomena in signaling and motility can be directly connected. Thus, the initial events in the association of a bacterium with a surface can be investigated in unprecedented detail in our collaboration.

The Team: The team represents a broad range of expertise that spans biological, chemical, physical, and computational sciences. Gerard Wong is an expert in experimental physics; his group has recently demonstrated algorithmic methods for massively parallel cell tracking in the context of bacterial communities. George O’Toole is a leading expert in the microbiology of bacterial biofilms. Berenike Maier has expertise in single molecule biophysics, and has made definitive force measurements on bacterial motility motors such as type IV pili. Ramin Golestanian has extensive expertise in theoretical physics and its application to biological systems, with a deep knowledge in fluids and polymers.