Ionizing radiation-induced DNA damage responses affect cell compressibility

Radiotherapy is an important treatment modality for cancer patients. Ionizing radiation kills cancer cells by inducing DNA damage. However, it remains unclear how this process affects the biomechanical properties of cells and how cellular mechanics affect DNA damage and repair. In this study, the effects of ionizing radiation on cell mechanics were investigated by precisely measuring the compressibility of cells in suspension using an in-house developed microfluidic device. We found that cell compressibility significantly increased after irradiation, depending on cell type and radiation dose. Radiation-induced DNA damage response (DDR) is an important process that alters cell mechanics, and this association was confirmed experimentally by inhibiting the DDR process. Furthermore, the mechanisms involved in changes in cell compressibility were investigated from the perspective of the nucleus and cytoplasm. Experiments showed that radiation reduced H3K9me3 staining intensity but had no effect on F-actin. This suggested that chromatin decondensation caused by radiation-induced DDR is the primary cause of changes in cell compressibility after radiation. The effects of cell mechanics on radiation-induced DNA damage were also investigated. The addition of blebbistatin reduced cytoskeletal forces on the nucleus, which resulted in a reduction in radiation-induced DNA damage. Collectively, this study elucidated reciprocal mechanisms of radiation-induced DNA damage and cell mechanics. (C) 2022 The Authors. Published by Elsevier Inc.

Automated summary

Radiotherapy is a crucial treatment for cancer patients, but its effects on cellular mechanics and DNA damage are still not well understood. In this study, the researchers investigated the impact of ionizing radiation on cell mechanics by measuring the compressibility of suspended cells using a microfluidic device. It was found that cell compressibility significantly increased after irradiation, and this was dependent on cell type and radiation dose. The study also revealed that the DNA damage response induced by radiation altered cell mechanics, and the primary cause of changes in cell compressibility was chromatin decondensation caused by radiation-induced DNA damage response.