Local force induced conical protrusions of phagocytic cells

Abstract

Magnetic tweezers were used to study the passive and active response of macrophages to local centripetal nanonewton forces on β1 integrins. Superparamagnetic beads coated with the β1-integrin-binding protein invasin were attached to J774 murine macrophages to mimic phagocytosis of bacterial pathogens. Forces exceeding ∼0.5 nN induce the active formation of trumpet-like protrusions resembling pseudopodia after an initial elastic deflection and a response time of ∼30 seconds. The speed of advancement of the protrusion is <v>=0.065±0.020 μm second-1 and is force independent. After saturation (after about 100 seconds) the protrusion stops abruptly and is completely retracted again against forces exceeding 5 nN with an effective relaxation time of ∼30 seconds. The active protrusion is tentatively attributed to the growth of the actin cortex in the direction of the force, and evidence for the involvement of actin is provided by the finding that Latrunculin A abolishes the activated cone growth. The growth is assumed to be activated by cell signaling mediated by the invasin-specific integrins (exhibiting β1 chains) and could play a role in phagocytic and protrusive events during immune response by macrophages.