Laser-Generated GHz Acoustic Waves Reveal a Universal Nuclear Stiffness Probed during Cell Differentiation

Abstract

Probing the mechanical properties of the nucleus is essential to understanding whole-cell mechanics under different physiological conditions. The nucleus has a complex composition yielding intricate rheological behavior that is appealing for measurements over a wide frequency range. However none of the existing techniques can exceed the kHz range. Moreover, the invasive nature of most of these techniques hampers the study of cell mechanics evolution during biological processes under physiological conditions. Here, we report the use of laser-generated GHz acoustic waves to probe the stiffness and viscosity of nuclei in single live cells. We demonstrate that the stiffness and viscosity reflect the compressional dynamics of the nuclear components. Furthermore we reveal the existence of a universal nuclear stiffness equal to 15 GPa in adult mammalian cells. We also emphasize the importance of Poisson's ratio in the describing the dynamic mechanical behavior of cells. Accordingly, we postulate that at GHz acoustical frequencies, anharmonic processes might occur in the cell in addition to thermally activated absorption processes already considered at low frequencies. On this basis, we demonstrate that the mechanical properties of the internal structure of the cell nucleus probed by GHz acoustic waves correlate with a specific gene expression pattern during cell differentiation. We suggest that the induction of differentiation synchronizes the stiffness of the cell nuclei. This analysis is supported by the observation of a new stress fiber organization around the nucleus and of an increased number of focal adhesions throughout the entire cell. The method described here is therefore capable of probing in a non-invasive manner the nanomechanical behavior of single live cell nuclei. This approach should open new areas in the investigation of physiological processes under biological conditions.