Fig. 1.

Interactions between individual innate immune cells and their targets. (A) Pseudocolor scanning electron microscopy images of fixed J774 macrophages engulfing antibody-coated beads: five 10 μm beads (upper image) and a 30 μm bead (lower image). Analysis of such images reveals that macrophages can expand their surface area by five-to-six times during the phagocytosis of large targets (Lam et al., 2009). (B) Live-cell studies using micropipette-held, initially quiescent human neutrophils that are brought into well-controlled contact with antibody-coated beads using a second pipette (not shown). This configuration eliminates interference from cell–substrate adhesion and, by imposing an essentially axisymmetric geometry, is much more amenable to quantitative analysis. Such analysis provides a wealth of information about the immunophysical behavior of innate immune cells, for example, the timelines of the cortical tension, cell–surface area and target position. The relative recording time of each image is included. (C) Computer simulations of ‘virtual cells’ are an integral part of an immunophysical analysis, enabling us to corroborate or discard hypotheses about the mechanoregulation of the responses of innate immune cells to pathogenic targets. The examples shown are from a simulation that reproduced not only the overall morphology of phagocytosis at the proper length scale (the scale bar represents 10 μm) but also the dynamics of this response (the simulation times are included), such as the time-dependent cortical tension, surface area and bead position. Moreover, the model predicted the density distribution of the cytoskeleton (encoded by color, with blue representing the lowest density and magenta the highest density). Scale bars: 10 μm.