Ionizing radiation-induced DNA damage responses affect cell compressibility.

Area of Science:

• Cellular Biology
• Biophysics
• Radiation Oncology

Background:

• Radiotherapy uses ionizing radiation to damage cancer cell DNA.
• The impact of radiation on cell mechanics and vice versa is not fully understood.

Purpose of the Study:

• To investigate how ionizing radiation affects cancer cell biomechanical properties.
• To explore the reciprocal relationship between cell mechanics and DNA damage/repair.

Main Methods:

• Precisely measured cell compressibility in suspension using a microfluidic device.
• Investigated mechanisms by inhibiting DNA damage response (DDR) and altering cytoskeletal forces.
• Assessed changes in H3K9me3 staining and F-actin.

Main Results:

• Cell compressibility significantly increased post-irradiation, varying by cell type and dose.
• Inhibiting DDR confirmed its role in altering cell mechanics.
• Chromatin decondensation, not F-actin changes, primarily caused altered compressibility.
• Reduced cytoskeletal forces decreased radiation-induced DNA damage.

Conclusions:

• Ionizing radiation alters cancer cell mechanics, primarily through radiation-induced DNA damage response and subsequent chromatin decondensation.
• Cellular mechanics reciprocally influence DNA damage, highlighting a feedback loop.
• Findings provide insights into radiotherapy efficacy and potential therapeutic strategies.