Mechanics of neutrophil phagocytosis: experiments and quantitative models

Abstract

To quantitatively characterize the mechanical processes that drive phagocytosis, we observed the FcγR-driven engulfment of antibody-coated beads of diameters 3 μm to 11 μm by initially spherical neutrophils. In particular, the time course of cell morphology, of bead motion and of cortical tension were determined. Here, we introduce a number of mechanistic models for phagocytosis and test their validity by comparing the experimental data with finite element computations for multiple bead sizes. We find that the optimal models involve two key mechanical interactions: a repulsion or pressure between cytoskeleton and free membrane that drives protrusion, and an attraction between cytoskeleton and membrane newly adherent to the bead that flattens the cell into a thin lamella. Other models such as cytoskeletal expansion or swelling appear to be ruled out as main drivers of phagocytosis because of the characteristics of bead motion during engulfment. We finally show that the protrusive force necessary for the engulfment of large beads points towards storage of strain energy in the cytoskeleton over a large distance from the leading edge (∼0.5 μm), and that the flattening force can plausibly be generated by the known concentrations of unconventional myosins at the leading edge.

Reorganization of the human neutrophil plasma membrane is associated with functional priming: implications for neutrophil preparations

“…A number of neutrophil studies have investigated changes in the bilayer structure of primed plasma membranes in the context of membrane raft formation or cortical change during the process of substrate adhesion [38], phagocytosis [39], morphologic polarization [40], and defined receptor-ligand interactions [41]. This study is unique in that it presents a physiologic snapshot of the changes that occur in neutrophil cortical structure following the in vitro exposure of blood cells to inflamed conditions likely to elicit the priming of circulating neutrophils within the vasculature.…”

Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

“…This has been clearly shown by a number of authors for spherical particles, where the size (radius) not only affects the internalization rate, the larger is the radius and the longer is the time for cell uptake, but it also affects the internalization mechanism (36)(37)(38). In a rough estimate, small particles (<500 nm) are internalized by receptor mediated endocytosis, a process requiring only a local modest rearrangement of the cell cytoskeleton; large particles (>1 μm) are internalized through a phagocytic process which conversely requires an extensive rearrangement of the cell cytoskeleton with the formation of protruding actin filaments; particles with an intermediate size (>500 nm and <1 μm) are thought to be internalized through a mixed mode.…”

Ammonia impairs neutrophil phagocytic function in liver disease

“…Several studies have defined the mechanisms involved in phagocytosis and show clearly that an increase in rounding of cells that is introduced by swelling would reduce its phagocytic function 31 (reviewed in Ref. 32). Furthermore, a similar reduction in phagocytic capacity following induction of hyponatremia, which is a well-known stimulus for cell swelling, argues for the role of cell swelling being an important mechanism involved in phagocytic dysfunction.…”