In vivo nuclear magnetic resonance (NMR) exposes living tissue to large magnetic fields. Tissue constituents interact weakly with magnetic fields, and the direct effects of magnetic fields on cellular, biochemical, and genetic processes have not been reproducibly established. However, microscopic ferromagnetic particles be present as contaminants in the lungs and other organs. in many occupational settings, humans inhale magnetic-particle aerosols; a fraction of the particles are retained in the lungs and are ingested by pulmonary macrophages. Strong magnetic fields can cause these magnetic particles to move, rotate, and agglomerate. The toxicology of NMR fields on cells and tissues containing ferromagnetic particles is unknown. Years 01 and 02 of the project demonstrated that microscopic magnetic particles can be observed both optically and magnetically in cells. Moreover, such particles can serve as an experimental indicator of macrophage function by noninvasively providing information on the motions of cell organelles. We found that for phagocytized particles, cytoplasmic motions rotate particles and produce detectable changes in the magnetic field. In addition, intracellular particles can be twisted by an applied external field, which allows measurement of cytosol viscoelasticity. The proposed researeh will examine magnetie field effects on particle-containing lung macrophages. In years 04-06 we will address the following questions: (1) Can magnetic forces overcome the motile forces generated by the macrophage cytoplasm? Can magnetic forces restrain chemotaxis? We will quantify the magnitude of traction forces magnetometrically. (2) Can motion imposed by magnet fields on magnetic-particle containing cell organelles modulate the fusion of phagocytic and lysosomal vesicles? (3) Can alterations in cell organelle motions, magnetometrically detected, be used to identify the existence and activity of an intracellular infection (e.g., AIDS) in macrophages? The goal is to examine how phagocytized ferromagnetic particles modify cell function when cells are exposed to strong magnetic fields. At the same time, we will measure the forces generated in cell motility, we will examine the role of organelle motions in phagolysosome processing, and we will identify changes in motion and rheology caused by viral infection.
