F-actin flashes on phagosomes mechanically deform contents for efficient digestion in macrophages

• Published in: Journal of cell science Vol. 133; no. 12
• Main Authors: Poirier, Mathieu B, Fiorino, Cara, Rajasekar, Thiviya K, Harrison, Rene E
• Format: Journal Article
• Language: English
• Published: England 24.06.2020
• Subjects: Complement; Macrophages; Phagocytosis; Phagosome maturation
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.239384

The mechanism and role of transient F-actin recruitment, or F-actin 'flashes', on phagosomes remains enigmatic. Here we provide a comprehensive characterization of F-actin flashing dynamics on phagosomes, including receptor and signaling involvement. F-actin flashes predominate during the integrin-driven complement receptor (CR)-mediated phagocytosis. F-actin flashes begin shortly after internalization and persist on phagosomes for approximately 3 minutes before disassembling and reassembling several times within the first hour. Strikingly, the appearance of F-actin flashes on phagosomes coincides with morphological deformation, lysis and occasional fission of internalized red blood cells. The cadence of flashes depends on particle stiffness, and the F-actin networks on phagosomes are enriched in mechanosensitive components including focal adhesion proteins, RhoA and actomyosin. Inhibiting Arp2/3 and myosin IIA activity significantly reduces the frequency at which phagosome cargo becomes deformed during transient F-actin accumulation. At later time points, post-F-actin flashing, enhanced degradation of phagosome contents is observed, compared with non-flashing phagosomes. Taken together, these data suggest that actomyosin-driven phagosome contractions serve to disrupt malleable particles physically, a process akin to mastication, to enhance later enzymatic digestion.