Mechanomedicine

Cells with aberrant force-generating phenotypes can lead to disease. The lab developed FLECS, a platform in which single-cell force sensors embedded in elastomers enable force measurements with roughly 100-fold improvement in throughput.

FLECS is scalable and integrates with the multi-well plate format, enabling highly parallelized time-course studies for the development of new therapies. We use it to analyze force generation issues underlying bronchoconstriction in asthma, cancer pathogenesis, cardiac insufficiency, and other areas of interest.

Cell state and identity are commonly characterized with biochemical markers, but biophysical markers are physiologically important integrative properties that can be rapidly assayed. Mechanical phenotypes such as cell size, shape, and response to applied loads can reveal nuclear and cytoskeletal organization, membrane integrity, osmotic pressure, and disease-linked cell state.

To measure cell mechanical phenotypes, our lab pioneered deformability cytometry, flowing single-cell suspensions in microfluidic devices and deforming the cells with surrounding fluid. High-speed cameras measure cells and their morphology when deformed at up to 2,000 cells per second.

We have also shown that magnetic nanoparticle-induced forces on cells can modulate calcium signaling in neurons and elicit long-term changes to ion channel expression. This mechanoceutical approach can be localized with magnetic field gradients or by embedding magnetic microparticles in hydrogel mediators of force.