Some cells of the immune system, or leukocytes, form a first line of defense by eating the microbes they encounter during a process called “phagocytosis.” Leukocytes spread around their prey and "swallow" it, before attacking it with aggressive chemicals. The arrival of micromanipulation techniques has made it possible to explore the mechanical aspects of phagocytosis, in particular by showing that during phagocytosis, a leukocyte becomes much stiffer. The role of this stiffening is still poorly understood, and even counterintuitive, because it could make it more difficult for the leukocyte to spread out and therefore limit the size of the targets that it can swallow. In our study, entitled “Distinct timing of neutrophil spreading and stiffening during phagocytosis,” we asked whether the spreading of the leukocyte during phagocytosis precedes or is simultaneous with its stiffening. We also tested whether leukocytes reach their maximum spreading area because of their increased stiffness or because their membrane stores are limited. To monitor both leukocyte spreading and mechanical changes during phagocytosis, we picked white blood cells one by one, gently aspirating them with a micropipette. To exert a known force on the cells and measure their stiffness, we pressed against them an ultra-flexible glass microfiber. We stimulated phagocytosis by feeding leukocytes with antibody-coated plastic microbeads. This allowed us to show that the relative timing of leukocyte spreading and stiffening depends on the size of their target: for smaller targets, spreading tends to precede stiffening, whereas for larger targets over which the leukocytes have more difficulty, spreading and stiffening tend to be simultaneous. Our observations also show that spreading does not stop due to the increased stiffness of the leukocyte, but when the latter reaches its limits in available membrane stores. Our study helps us to better understand the complex defense mechanism that is phagocytosis.

The cover image of the April 19 issue of the Biophysical Journal is an artistic rendering of these experiments. It represents an immune cell held by a micropipette and phagocytosing an antibody-covered microbead. Julien Husson rendered this image by using the free 3D software blender (https://www.blender.org/), trying to mimic the look of scanning electron microscopy images. You can find more of our publications and more of Husson’s 3D art on his web page: https://cellmechanics.jimdofree.com/.

- Alexandra Zak, Sophie Dupré-Crochet, Elodie Hudik, Avin Babataheri, Abdul I. Barakat, Oliver Nüsse, and Julien Husson