Abstract
Encounters between human neutrophils and zymosan elicit an initially protrusive cell response that is distinct from the thin lamella embracing antibody-coated targets. Recent experiments have led us to hypothesize that this behavior has its mechanistic roots in the modulation of interactions between membrane and cytoskeleton. To test and refine this hypothesis, we confront our experimental results with predictions of a computer model of leukocyte mechanical behavior, and establish the minimum set of mechanistic variations of this computational framework that reproduces the differences between zymosan and antibody phagocytosis. We confirm that the structural linkages between the cytoskeleton and the membrane patch adherent to a target form the “switchboard” that controls the target specificity of a neutrophil's mechanical response. These linkages are presumably actin-binding protein complexes associating with the cytoplasmic domains of cell-surface receptors that are engaged in adhesion to zymosan and Fc-domains.
Highlights
Our recent quantitative comparison of the physical responses of human neutrophils to zymosan and to antibody-coated targets has exposed differences between these two forms of phagocytosis [3]
Since the cortical tension is the dominant driver of target inward motion, a conserved targetinternalization speed implies that the cytoplasmic viscosity rises concurrently with the cortical tension during phagocytosis, in agreement with a previously reported tight balance between the cortical tension and cytoplasmic viscosity of leukocytes [4]
We hypothesized that structural interactions between the cytoskeleton and the membrane patch adherent to a target play a pivotal role in the control of this target specificity
Summary
Our recent quantitative comparison of the physical responses of human neutrophils to zymosan (an insoluble, particulate fraction from yeast cell walls and prominent model system in the study of fungal infection [1,2]) and to antibody-coated targets has exposed differences between these two forms of phagocytosis [3]. The quantitative measure that most clearly illustrates this difference is the distance over which a neutrophil initially pushes an adherent target outwards (Fig. 1A). This pushout distance is 1.0360.3(SD) mm in the case of zymosan, versus 0.1260.14(SD) mm for antibody-coated targets. The experiments provided the maximum cortical tension of neutrophils and the fastest speed of target inward motion during the two forms of phagocytosis. A ,two-fold difference in cortical tension (0.3 mN/m versus 0.14 mN/m, with the higher value observed during zymosan engulfment) contrasts with an indistinguishable target speed (,33 nm/s) in the two cases. Since the cortical tension is the dominant driver of target inward motion, a conserved targetinternalization speed implies that the cytoplasmic viscosity rises concurrently with the cortical tension during phagocytosis, in agreement with a previously reported tight balance between the cortical tension and cytoplasmic viscosity of leukocytes [4]
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