Cell nucleus is crucial for controlling gene expression. Recent studies have shown that the extra- and intra-cellular mechanical factors, as well as conventionally known chemical factors, affect gene expression pattern [1]. In the mechano-signaling process, the mechanical forces are reported to be transmitted to the cell nucleus via the actin cytoskeleton [2]. The cell nucleus behaves as viscoelastic materials. Thus, to further understand nuclear mechanotransduction, we focused on the dynamic properties of the forces acting on the nucleus, and the intranuclear viscoelasticity that determines the nuclear responsiveness to temporally dynamic mechanical forces.

We have developed a method to manipulate the spatiotemporal properties of mechanical forces on the nucleus by controlling actin dynamics through the control of cell migration with micro-structured cell culture substrate. The dynamic mechanical forces acting on the nucleus were successfully differently controlled depending on whether the substrate structure consists of micro-pillars or micro-pits.

As for the intranuclear viscoelasticity, we applied particle tracking microrheology [3] with fluorescence microbeads with 200 nm in diameter to quantify the intranuclear storage and loss moduli, G′ and G′′, on the mesoscale that corresponds to the assembled chromatin. In the cells toward osteogenic differentiation, the G′ and G′′ were decreased toward the middle stage and maintained low in the late stage of differentiation with an increase in loss tangent [4]. In addition, the measurement under the condition with the chromatin and actin perturbations suggested that the chromatin was a determinant of the G′ and G′′, and the mechanical forces acting on the nucleus contributed to condense and decondense chromatin in undifferentiated and early differentiation stages, respectively.

Our next step to clarify the nuclear mechanotransduction is to analyze the relationship among the spatial pattern of gene expression in the nucleus, intranuclear structural and mechanical properties, and actin dynamics.

[1]   Uhler C. and Shivashankar G. V. (2017) Nat. Rev. Mol. Cell Biol. 18, 717-727.

[2]   Miyoshi H. and Adachi T. (2014) Tissue Eng. B. 20, 609-627.

[3]   Mason T. G. (2000) Rheol. Acta. 39, 371-378.

[4]   Matsushita K. et al. (2021) FASEB J, 35, e22071.