Measuring and manipulating cell mechanics to diagnose and treat disease
Similarly, cells with aberrant force-generating phenotypes can lead to disease. Therefore, our lab has developed a platform called FLECS in which single-cell force sensors embedded in elastomers enable force measurements with ~100-fold improvement in throughput than was previously possible. The microtechnology is scalable and integrates with the multi-well plate format, enabling highly parallelized time-course studies for the development of new therapies. We are continuing to use the platform to analyze force generation issues that underlie bronchoconstriction in asthma, pathogenesis of cancer, cardiac insufficiency, and other areas of interest.
Cell state and identity is commonly characterized with biochemical markers, but biophysical markers are physiologically important integrative properties which can be rapidly assayed. Mechanical phenotypes that include cell size, cell shape, and response to applied loads can reveal the nature of internal properties such as nuclear and cytoskeletal organization, membrane integrity, and osmotic pressure. These measurements are useful in understanding the identity and internal state of cells, which can be used to discriminate types of cancer cells, activated immune cells, stem cells, or cell cycle stages.
To measure cell mechanical phenotypes, our lab has pioneered deformability cytometry, wherein we flow single-cell suspensions in microfluidic devices, and deform the cells with the surrounding fluid. We use high-speed cameras to measure the cells and their morphology when deformed, up to 2,000 cells per second. We are continuing to investigate how the internal structure of cells contributes to their holistic mechanical properties, and how this can be used to further medical diagnoses and treatments.
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We have also shown that magnetic nanoparticle-induced forces on cells can be used to modulate calcium signaling in neurons and elicit long-term changes to ion channel expression levels. This mechanoceutical approach can be localized by focusing strong magnetic field gradients with local magnetic materials or through embedding magnetic microparticles in hydrogel mediators of force.
Di Carlo D, Tseng P, and Pushkarsky I. “Device and methods for force phenotyping of cells for high-
throughput screening and analysis.” U.S. Patent No. 10082497.
Di Carlo D, Gossett D, and Tse H. "Method and device for high throughput cell deformability
measurements." U.S. Patent Nos. 8935098, 9897532, E.P. Patent No. 2619545
Di Carlo D, Gossett D, Tse H, and Chung A. "System and method for deforming, imaging and analyzing
particles." U.S. Patent Nos. 9464977, 9638620, 10107735, 10295455, Japanese Patent No. 6396305.