Mechanical characterization of cancer cell nuclei in situ

Abstract

While reduced whole cell stiffness has long been used to identify cancerous cells, cancer progression usually results in enhanced nuclear deformability as well. However, previous studies on nuclear mechanical properties were conducted either on isolated nuclei or intact nuclei indirectly, and intracellular characterization in situ has been missing. In this paper, an AFM technique to study nuclear mechanics in situ is shown. Using this technique we demonstrated that isolated nuclei exhibited significantly lower Young's moduli than intact nuclei in situ (8.64 ± 1.36 kPa vs. 78.46 ± 14.88 kPa, p=0.0001), and we characterized and compared the mechanical properties of nuclei in situ between RT4 and T24 cells with different metastatic potential. It was quantitatively demonstrated that the cell nuclei were significantly stiffer than the cytoplasm, and that intact nuclei of RT4 exhibited significantly higher stiffness than that of T24 cells (8.4 ± 1.02 kPa vs. 5.67 ± 0.48 kPa, p<0.03). These results may provide insight into the mechanisms by which the nuclear mechanics influences cell function, contributing to cancer development.