The effects of the mechanical trapping of the nucleus on cellular UV resistance using a micropillar substrate

Abstract

DNA damage induced by the radiation, including ultraviolet (UV) light, exerts adverse effects on genome stability, alters the normal state of life, and causes many kinds of diseases. Thus, a biochemical or biomechanical method in DNA damage repair and protection is well required. Hear we investigated the effects of mechanical factors, such as mechanical deformation of the nucleus, on UV radiation resistance of DNA in epithelial-like cells derived from Xenopus laevis (XTC-YF). XTC-YF cells spread normally in the spaces between micropillars whose diameter, length, and center to center spacing was 3, 9, and 9 μm, respectively. Their nuclei showed remarkable deformation and appeared to be “trapped” mechanically on the array of pillars. We compared the cells cultured on the normal flat substrates and on the pillar substrates and found that the UV radiation-induced DNA damage estimated by the fluorescent intensity of the phospho-histone γ-H2A.X, was significantly inhibited in the cells cultured on the pillar substrates. The significant positive correlation was observed between fluorescent intensity of intranuclear DNA and γ-H2A.X in the cells cultured on the flat substrates following UV irradiation, while in the cells on the pillar substrate, their correlation became lower. These results indicate that the inhibition of UV radiation-induced DNA damages might be resulted from structural change of DNA caused by the mechanical stress of the nucleus of the cells on the pillars. Our study first demonstrated the nuclear stress-induced inhibition of DNA damages in living cells.

Keywords

• cell biomechanics
• mechanobiology
• nuclear mechanotransduction
• dna damages
• microfabrication