The atomic force microscope (AFM) was used to quantify micromechanical properties (i.e., localized to an area of approximately 0.015 microns 2) of cultured rat atrial myocytes. Quiescent cells in calcium-free solution were quite compressible over the nuclear region, e.g., a force of 3-4 nN produced 180-225 nm cell indentation. Transverse stiffness of quiescent cells increased by approximately 2-fold after an increase in extracellular calcium from 0 to 5 mM and by approximately 16-fold after fixation with Formalin. There was five- to eightfold variation in stiffness of quiescent cells over the cell surface, such that stiffness was lowest over the nuclear region, and it increased toward the cell periphery. These regional variations correlated with the cytoskeletal heterogeneity as revealed by the AFM and fluorescence imaging. Localized contractile activity of beating cells could be monitored in terms of the surface deformation with high transverse spatial (approximately 1-3 nm) and temporal (60-100 microseconds) resolutions. Alterations in cell contractile activity with physiological perturbations and dynamic changes in cell stiffness during a single contraction could be observed. These results demonstrate the feasibility of AFM-based characterization of highly localized cellular micromechanical properties. Relationships among localized cell mechanical behavior and the underlying biochemical and/or structural environment, a crucial aspect in understanding cellular (dys)function, can now be directly examined.

Shroff, S. G., Saner, D. R., & Lal, R. (1995). Dynamic micromechanical properties of cultured rat atrial myocytes measured by atomic force microscopy. American Journal of Physiology-Cell Physiology, 269(1), C286–C292.