Micropipette-based tools to probe cellular and intracellular mechanics: from immune cell activation to cell adhesion and rupture, to the mechanics of mitochondrial fission

Probing single-cell mechanics requires sensitive force probes. Although established techniques such as optical tweezers and atomic force microscopy are powerful tools, when performing cellular-scale studies, they do not systematically cover the relevant range of forces or stiffness, nor do they always provide enough versatility to allow observing the cells while probing them. This leaves room for custom-made and cost-effective approaches. Here I will start by briefly describing various techniques that we have developed to probe the mechanics of adherent and non-adherent cells. These techniques are based on micropipettes, a tool that, although introduced almost a century ago, still allows for development and provides a powerful tool for quantitative measurements. Using these tools, we have measured forces generated by immune cells during activation and shown that leukocytes become stiffer during activation. Furthermore, by aspirating adherent cells, we could quantify cell-substrate adhesion, and by compressing adherent cells with controlled forces, we could establish a criterion for membrane rupture. In a second part, I will explain how, by rupturing the plasma membrane of a cell using micropipettes, we could induce an immediate fission of all mitochondria within this cell, not unlike what occurs during cell infection by specific toxins. By modeling mitochondrial mechanics using fluid mechanics approaches, we could explain the typical size of mitochondria after fission and the role of mitochondrial morphology in the occurrence of fission events