Quantifying the mechanical properties of cells is important for better understanding how mechanics constrain and regulate cellular processes. Furthermore, because pathologies often correlate with altered cell mechanical properties, mechanical parameters can be used to characterize the pathological state of cells. Both cell tension and cell viscoelasticity (representing the average of the cell bulk) can contribute to cell stiffness, which quantifies how a cell deforms when it is subjected to a force. It is unclear which of these features is the most relevant or whether both should be included. Experimentally, cell stiffness is often determined by performing micro- or nanoindentation on cells, often by using atomic force microscopy (AFM). AFM indentation leads to a well-known paradox: indenting cells with sharp tips leads to an overestimation of the stiffness compared with values obtained when indenting with a bead of a size comparable to the cell size. To understand to what extent cell tension and viscoelasticity contribute to cell stiffness and to show that this can resolve this apparent paradox, we performed profile microindentation experiments on cells by using a technique that we have developed in the lab over the years. We use flexible micropipettes as cantilevers. Micropipettes are versatile tools that can be modified by using a microforge. See examples of videos online where we show how we cut micropipettes to a desired diameter and melt their tip into a bead of the desired diameter (https://cellmechanics.jimdofree.com/videos/). In our work, we use modified micropipettes with a bead or a needle at their tips and press these tips against cells held by stiff micropipettes, as shown in the cover image of the January 16 issue of Biophysical Journal. This image was created by Julien Husson with Blender (https://www.blender.org/), a very complete, free, and open source software. Plenty of high-quality paid and free tutorials are available online, including a famous series that enables the user to create a 3D donut (https://www.youtube.com/playlist?list=PLjEaoINr3zgEPv5y--4MKpciLaoQYZB1Z). This might not be relevant for a scientist as an object to create, but very much so as an exercise to master the creation process, leading to the rendering of a detailed and realistic 3D scene. This cover image was then painted by using a 2D illustration application (Photoshop) to add details and texture to the cells without requiring further 3D modeling. More illustrations created with Blender can be found on Julien Husson’s website (https://cellmechanics.jimdofree.com).

— Olga Markova, Christophe Clanet, and Julien Husson