Three-Dimensional Cellular Raman Analysis: Evidence of Highly Ordered Lipids Within Cell Nuclei

Striking levels of spatial organization exist among and within interphase cell chromosomes, raising the possibility that other nuclear molecular components may also be organized in ways that facilitate nuclear function. To further examine molecular distributions and organization within cell nuclei, we utilized Raman spectroscopy to map distributions of molecular components, with a focus on cellular lipids. Although the vast majority of cellular lipids are associated with membranes, mapping the 2870/2850 cm^-1 lipid peak ratios revealed that the most highly ordered lipids within interphase cells are found within cell nuclei. This finding was seen in cells from multiple tissue types, noncancerous cells, and in cancer cell lines of different metastatic potential. These highly ordered lipids colocalize with nuclear chromatin, are present throughout the nuclear volume, and remain colocalized with chromatin through mitosis, when the nuclear envelope has dissociated. Phosphatidylinositol is a major component of the highly ordered lipids. The presence of phosphatidylinositol and other lipids in the nuclear interior is well established, but their highly ordered packing has not been reported and represents a unique finding. The molecular interactions involved in the formation and maintenance of these highly ordered lipids, and their potential effects on nuclear activities, remain to be discovered.