Dynamic AFM elastography reveals phase dependent mechanical heterogeneity of beating cardiac myocytes

We developed a novel atomic force microscope (AFM) indentation technique for mapping spatiotemporal stiffness of spontaneously beating neonatal rat cardiac myocytes. Cells were indented at a rate close but unequal to their contractile frequency. Resultant apparent elastic modulus cycled at a predictable envelope frequency between a systolic value of 26.2 plusmn 5.1 kPa and a diastolic value of 7.8 plusmn 4.1 kPa. In cells probed along their axis, spatial heterogeneity of systolic stiffness correlated with the sarcomeric structure of underlying myofibrils. Treatment with blebbistatin eliminated contractile activity and resulted in a uniform modulus of 6.5 plusmn 4.8 kPa. The technique provides a unique means of probing the mechanical effects of disease processes and pharmacological treatments on beating cardiomyocytes at the subcellular level, providing new insights relating myocardial structure and function.