Role of Tensile Stress in DNA Nanoresonators for Epigenetic Studies

The evaluation of epigenetic features such as DNA methylation is becoming increasingly important in many biochemical processes like gene expression and transcription as well as in several diseases like schizophrenia or diabetes. Here, we report that self-assembled nanomechanical resonators entirely composed of DNA molecules can be used to explore gross changes in DNA methylation levels (0-25-50%), while careful control of tensile stress is needed to reduce the variability of resonance frequency for rigorous quantification. The effect of the tensile stress retained by the suspended DNA nanoresonators on the application of the technique is extensively explored using a combination of laser Doppler vibrometry and atomic force spectroscopy. DNA nanoresonators are real-time, label-free sensors and could avoid chemical functionalization and sample amplification. Therefore, they may represent in the future a key complementary routine tool for global DNA methylation analysis needed to evaluate the consequences of environmental stresses on the human genome.