Nucleus regulates cellular functions not only by controlling biochemical signals but also by adjusting its mechanical properties to protect DNA from forces arising from the interaction with surrounding environment and neighbor cells. Recent studies have demonstrated that alterations in the mechanical properties of the nucleus are indicative of its structural remodeling, which in turn influences cellular functions. Therefore, measurements of the time-dependent nuclear mechanical properties are crucial for mechanobiology field. However, conventional techniques such as cantilever compression and optical tweezers cause serious cell damage, making it difficult to perform long-term measurements on the same cell. Here, we have developed a focused acoustic-radiation-force microscopy, which generates the localized acoustic-radiation force around the nucleus to deform the nucleus without mechanical contact, laser irradiation, and staining. The radiation force was induced by the amplitude-modulated ultrasound at the modulation frequency of near 1 Hz, and the nucleus cyclic deformation of the nucleus was observed with the optical microscopy. We analyzed the phase delay of the nuclear deformation and the strain amplitude to investigate the nucleus viscoelasticity changes for 60 min. Then, we applied the method to the selective noninvasive nucleus mechanical stimulation and found that it promoted nucleocytoplasmic transport using the nuclear staining reagent.
Fujiwara et al. (2025) studied this question.