Comparison of the Phagocytosis Mechanics of Neutrophils, Monocytes, and Macrophages

Abstract

We investigate whether different types of immune cells-human neutrophils, monocytes, and murine J774 macrophages-employ a universal mechanistic program during phagocytosis, or if there are quantitative or even qualitative differences in the manner these professional phagocytes engulf pathogens. Following a detailed characterization of the baseline mechanical properties of passive cells, we examine their active mechanical behavior during one-on-one encounters with two different types of target: antibody-coated beads of various sizes, and serum-opsonized zymosan particles. Our immunophysical approach integrates dual-micropipette experiments using individual live cells with finite-element computer models of autonomous leukocyte deformation. With the exception of a striking difference in the regulation of the cortical tension, we find that the mechanical process of the engulfment of antibody-coated beads is essentially the same between the three cell types. In contrast, for zymosan phagocytosis, we identify critical differences between neutrophils on the one hand, and monocytes/macrophages on the other hand. Whereas neutrophils extend a focused pseudopod that pushes the zymosan particle outwards before engulfment, monocytes and macrophages generate a broad patch of frond-like ruffles which appear to entangle and eventually overgrow the zymosan. These and other quantitative insights provided by our experimental/theoretical approach not only deepen our fundamental understanding of innate immunity, but also illuminate the mechanisms underlying eukaryotic cell motility.