Apr 15, 2020

Spatio-temporal mapping of mechanical force generated by macrophages during FcγR-dependent phagocytosis reveals adaptation to target stiffness

BioRxiv : the Preprint Server for Biology
P. Rougerie, Dianne Cox


Macrophage phagocytosis is a strikingly flexible process central to pathogen clearance and is an attractive target for the development of anti-cancer immunotherapies. To harness the adaptability of phagocytosis, we must understand how macrophages can successfully deform their plasma membrane. While the signaling pathways and the molecular motors responsible for this deformation have been studied for many years, we only have limited insight into the mechanics that drive the formation of the phagocytic cup. Using Traction Force Microscopy (TFM), we have been able to characterize the spatio-temporal dynamics of mechanical forces generated in the course of Fc{gamma}R-dependent frustrated phagocytosis and we determined whether this was affected by the stiffness of the potential phagocytic targets. We observed that frustrated phagocytosis is an atypical form of spreading where the cell deformation rate is unaffected by the substrate stiffness. Interestingly, the cell initially extends without forces being recorded then switches to a mode of pseudopod extension involving spatially organized force transmission. Importantly we demonstrate that macrophages adapt to the substrate stiffness primarily through a modulation of the magnitude o...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Diabetes Mellitus, Non-Insulin-Dependent
Research Subject
Korean Race
Single Nucleotide Polymorphism
Gene Mutant

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