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2 integrins impose a mechanical checkpoint on macrophage phagocytosis

ABSTRACT: Phagocytosis is an intensely physical process that depends on the mechanical properties of both the phagocytic cell and its chosen target. Here, we employed differentially deformable hydrogel microparticles to examine the role of cargo rigidity in the regulation of phagocytosis by macrophages. Whereas stiff cargos elicited canonical phagocytic cup formation and rapid engulfment, soft cargos induced an architecturally distinct response, characterized by filamentous actin protrusions at the center of the contact site, slower cup advancement, and frequent phagocytic stalling. Using phosphoproteomics, we identified 2 integrins and their downstream effectors as critical mediators of this mechanically regulated phagocytic switch. Indeed, comparison of wild type and 2 integrin deficient macrophages indicated that integrin signaling acts as a mechanical checkpoint by shaping filamentous actin to enable distinct phagocytic engulfment strategies. Collectively, these results illuminate the molecular logic of leukocyte mechanosensing and reveal potential avenues for modulating phagocyte function in immunotherapeutic contexts.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow

SUBMITTER: Zhuoning Li

LAB HEAD: Morgan Huse

PROVIDER: PXD049434 | Pride | 2024-08-22

REPOSITORIES: Pride

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			Action	DRS
	1809AS_S1_12Fr_HpHKit_Total_i39_MorganHuse_All_Peptides.xlsx	Xlsx
	1809AS_S1_12Fr_HpHKit_Total_i39_MorganHuse_All_Proteins.xlsx	Xlsx
	1809AS_S1_6Fr_Phos_i39_MorganHuse_All_Phospho_Peptides.xlsx	Xlsx
	1809AS_S1_6Fr_Phos_i39_MorganHuse_All_Proteins.xlsx	Xlsx
	1809AS_S1_Fr10_HpHKit_Total_i39_MorganHuse.raw	Raw

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