Low-Frequency Label-Free Raman Imaging of Cells

Conformation and compaction of nucleic acids (NAs), particularly DNA, are vital for any organism but are poorly studied in vivo because of the absence of noninvasive techniques. In this study, we introduce label-free low-frequency (LF) Raman imaging for mapping NA conformation and compaction in eukaryotic cells. Specifically, we find that the LF Raman spectrum in the nucleus strongly differs from that in the cytoplasm: first, by the prominent π-band indicating the ordered arrangement of nucleotides and second, by the low intensity highlighting the compact DNA packing. Using low-frequency imaging, we also reveal the difference in NA packing in normal cells and cells with DNA damage. The proposed technique is expected to complement widely used high-frequency Raman imaging: while the latter tells us "what is there?", our approach answers the question "how is it organized?", which is of paramount importance for cell biology. Moreover, this approach can be extended to studying other complex biomolecular systems.