Magnetic nanoparticles have been widely used in life science research and medicine. Such particles are used for construction of biosensors, as well as for detection of important immune or cancer cells from physiological samples. Currently, magnetic particles must be synthesized through chemical processes, and proteins or other targeting components are added to particle surfaces through painstaking step-by-step processes. Nature has also developed an approach to biomineralize magnetite to create magnetic nanoparticles. Several species of ?magnetotactic? bacteria evolved to produce chains of magnetic nanoparticles in specialized compartments called magnetosomes that aid in alignment within Earth?s magnetic field. These bacteria may be ideal factories for the next-generation of low cost magnetic particles that are pre-coated with medically useful proteins. We will use microfluidic tools to apply selection pressures for directed evolution of magnetotactic bacteria with a range of magnetosome properties. We will also develop techniques to isolate magnetosomes from the selected cell populations while maintaining the commercially useful protein and lipid envelope surrounding the precipitated magnetite particles. Besides use in creating customized and potentially economical protein-coated nanoparticles for biosensing, imaging, and cell biology research, the genetic changes within our evolved strain will give unique insights into biomineralization, vesicle formation, and self-assembly processes that can be used in a variety of biological systems.
Today, many powerful techniques in science and medicine are enabled by magnetic nanoparticles – tiny chunks of magnetic material that can be tracked on an MRI, and manipulated with external magnetic fields. Traditionally, these particles have been produced by expensive chemical means, resulting in particles that are high-cost and generally non-uniform. Alternative methods for magnetic nanoparticle production have the potential to extend these applications by decreasing costs of healthcare and basic science research. Nature, it turns out, has some tricks up its sleeve. Some naturally-occurring bacteria such as Magnetospirillum magnetotacticum produce their own magnetic nanoparticles in order to enable them to sense their orientation relative to the Earth's natural magnetic field. These nanoparticles (referred to as "magnetosomes" - magnetic bodies) are of consistent size and chemical composition, making them ideal for scientific use. Moreover, they come pre-wrapped in a stabilizing lipid bilayer, which prevents clumping and provides attachment points for adding additional useful proteins and drugs. We know how to genetically modify M. magnetotacticum to attach proteins of interest to the surface of its magnetosomes, but we don't know how to change the size of the particles that the bacterium produces. Thankfully, there is another trick we can borrow from nature to do this. By providing an appropriate selective pressure, we can evolve new strains of M. magnetotacticum to produce slightly larger or smaller nanoparticles, even without knowing which specific genetic changes need to happen to achieve this. Eventually, a library of bacterial strains could be produced with whatever production capabilities are desired. In this project, we worked on developing tools for generating such libraries, by selectively growing bacteria with specific magnetic properties and discarding their competitors. With optimization and further development of these techniques, it may be possible to simply grow magnetic nanoparticles of the future in large vats, without human intervention, using the living chemical factories of biological cells.
