Biomechanical Characterization of Human Pluripotent Stem Cell-Derived Cardiomyocytes by Use of Atomic Force Microscopy.

Atomic force microscopy (AFM) is not only a high-resolution imaging technique but also a sensitive tool able to study biomechanical properties of biosamples (biomolecules, cells) in native conditions-i.e., in buffered solutions (culturing media) and stable temperature (mostly 37°C). Micromechanical transducers (cantilevers) are often used to map surface stiffness geometry, elastic, and contact parameters of living cells; however, they can also be used to monitor time course of dynamic forces (beating), their rate, and other biomechanical properties of cardiomyocyte contractility. Here we describe the construction of an AFM-based biosensor setup designed to study the biomechanical properties of cardiomyocyte clusters, using standard uncoated silicon nitride cantilevers. Force-time curves (mechanocardiograms, MCG) are recorded natively and in the presence of cardiomyocyte-contraction-affecting drugs (e.g., isoproterenol, metoprolol) in the medium, under physiological conditions. The average value of contraction force and the beat rate as basic biomechanical parameters represent pharmacological indicators of different phenotype features. Robustness, low computational requirements, and optimal spatial sensitivity (detection limit 200 pN or 20 nm) are the main advantages of the presented method.