High-throughput methods for measuring mechanical properties of cells are ready for prime time.

The cytoskeleton, cell membrane, cytoplasm and embedded organelles give rise to the mechanical properties of cells, and these properties inform cellular state and functions. Changes in biomechanical properties can go hand in hand with developmental changes or even transformations of healthy cells into cancer cells.

Cell squeezing through a constriction in a microfluidic channel. Credit: Debbie Maizels/Springer Nature

Traditional methods for assessing the viscoelastic properties of cells include atomic force microscopy, optical tweezers or micropipette aspiration. However, these approaches can only be applied to one cell at a time, and throughput is therefore typically low — on the order of tens to hundreds of cells per hour. In recent years, a variety of alternatives to these approaches have emerged that can be classified under the umbrella of deformability cytometry (for example, Proc. Natl Acad. Sci. 109, 7630–7635, 2012; Proc. Natl Acad. Sci. 110, 7580–7585, 2013; Nat. Methods 12, 199–202, 2015). These new kids on the block are mainly based on microfluidic approaches, and they can reach a throughput of thousands to millions of cells per hour.

In one class of approaches, cells squeeze through constrictions in microfluidic channels, and the cells’ time to pass through the constriction correlates with the mechanical properties of the cells. Other approaches are contactless and induce deformations through flow and/or pressure gradients while deformations are read out via high-speed imaging.

Deformability cytometry approaches measure the cumulative viscoelastic properties of individual cells. As the various forms of deformability cytometry operate with different geometries and under different stress and strain rates, the techniques may be sensitive to different aspects of a cell’s biomechanics. However, this is no different from the more traditional methods (Nat. Methods 15, 491–498, 2018); the choice of method needs to be informed by the experimental question. More importantly, these differences may offer opportunities to gain insights into the underlying principle of cellular mechanics.

Microfluidics-based approaches are more accessible than the traditional approaches for measuring mechanical properties, and several deformability cytometry methods have been or are being commercialized. We expect to see uptake of these approaches in the broader community and look forward to their application to a wide range of questions.