Simultaneous Imaging of Dynamics and Biochemical Activities of Single Phagosomes

Abstract

Phagocytosis is a major defense mechanism used by our immune system to eliminate pathogens. It proceeds in multiple steps: ligand-receptor recognition between pathogens and cell membranes in the beginning, internalization of pathogens into intracellular membrane organelles known as phagosomes, transport of phagosomes from cell edge to areas surrounding the cell nucleus, and digestion of the encapsulated pathogens through series of chemical reactions. All those steps must occur in the right order at the right time and in the right subcellular location. Abnormalities in any of those steps can lead to progression of infections and other serious human diseases, such as cystic fibrosis and chronic granulomatous disease. Thus, a fundamental understanding of phagocytosis is critical for developing methods to diagnose and treat those diseases. Unfortunately, that has been a grand challenging due to the complexity of the mechanisms involved in phagocytosis. To address the critical need, we developed nanoparticle-based sensors to probe the chemical and dynamical activities during phagocytosis. Simultaneous measurements of phagosome transport, acidification, and fusion reveal a striking correlation between the intracellular transport of phagosomes and their biochemical activities during maturation. Our results reveal a regulatory mechanism underlying the orchestration of dynamical and biochemical signaling processes during phagosome maturation.