Escherichia coli chemotaxis: experiments and models of cell motility in 2D confined space & helical flagella in 3D space
Title: Escherichia coli chemotaxis: experiments and models of cell motility in 2D confined space & helical flagella in 3D space
Students: Joshua Cohen, Cameron McKay and Charlie Stein
Advisors: Dr. Frank Healy and Dr. Hoa Nguyen
Abstract: Many organisms rely on motility for survival, e.g., in the quest for food or predator avoidance. Bacteria such as Escherichia coli possess extracellular helical appendages known as flagella that, through the rotary action of membrane-bound “nanomotors”, propel the organism through aqueous environments. Motility is governed by the presence or absence of gradients of chemical attractants or repellents. In order to navigate toward higher concentrations of attractants, bacteria perform a biased random walk characterized by an alternating sequence of runs and short-lived, re-orienting tumbles. For example, in the presence of an attractant gradient, behavior is biased toward longer runs in the direction of increasing attractant; conversely, in the presence of repellents, tumbles are more frequent, as bacteria seek suitable “escape routes”. This biased random walk behavior has attracted interest for biomedical and other applications. It is envisioned that small devices might be engineered that utilize bacterial motility mechanisms to swim to specific destinations and deliver payloads. For example, a nanodevice could carry an antitumor drug to tumor tissue sites in the body, ideally increasing specificity and minimizing off-target effects of current chemotherapy treatment methods. The design of such devices would be greatly facilitated by a thorough understanding of motility mechanics. The objective of this work is to bring together experimental bacterial motility data and mathematical models to more fully understand and accurately simulate motility. We are using confocal microscopy-based chemotaxis assays with motile strains of E. coli carrying plasmid-encoded green fluorescent protein gene (gfp) or a gfp deriviative. In conjunction with the experimental approach, we are simulating motility in 2D space with different boundary conditions and obstacles, and simulating the flagellar dynamics in 3D space, with the long term goal of generating a unified model of bacterial motility in complex environments.
For 2D simulations, we model E. coli hydrodynamic movement toward a food source (chemotaxis) in a confined space with and without obstacles. This can be achieved by coupling the intracellular signaling pathway RapidCell (RC) model with the cell motility in a fluid using the Lattice Boltzmann Method (LBM). The LBM also allows for the simulation of boundaries and obstacles, and therefore yields a more realistic simulation of E. Coli chemotaxis when coupled with RC.
For 3D simulations, we examine how E coli use their helical flagella to move through fluid environments toward areas of high nutrient concentrations (chemotaxis). If all the flagella rotate counterclockwise, they bundle together and made the cell propel forward in a certain direction (called a “run”). Conversely if one of the flagella rotates clockwise, the flagella unbundle and the cell can reorient itself in a different direction (called a “tumble”). We model the run/tumble movement of a cell propelled by a flexible flagellum within a three dimensional nutrient concentration gradient. This is achieved by coupling the helical flagellar Kirchhoff Rod Model with the structure-fluid interactions using the Method of Regularized Stokeslets and the intracellular signaling pathway RapidCell (RC) model. Our simulations provide insights into the flagellar mechanism and how it aids the cell in moving through its environment.