Thursday, April 25, 2024
4/25/2024
Abstract Cancer is known to be associated with genetic mutations. Evidences suggest that these genetic changes lead to increased structural disorder in biological cell nuclei. This disorder is believed to result from alteration and rearrangement of DNA molecular mass density at the beginning. In the case of progressive carcinogenesis, such changes occur at length scales ranging from nano- (<100nm) to submicron (>100nm) scales. Consequently, it has been recognized that measurement and quantification of these structural changes could, therefore, be a potential cancer biomarker. Accordingly, some recent studies based on partial wave spectroscopy and other nano-optical techniques have quantified the nanoscale structural properties in cells. However, these techniques are still in the early stages and require complicated new experimental setup, thus limiting access to these studies to only a handful of research groups in the biomedical and biological sciences. Meanwhile, the use of existing optical techniques, e.g., confocal microscopy, to conduct such studies is still unexplored. In view of that, we have developed a novel method, by combining confocal microscopy imaging and a technique borrowed from mesoscopic physics, termed as inverse participation ratio (IPR) technique, or simply the “IPR technique”, to measure and quantify the degree of structural disorder in cell nuclei. Components of the cellular matrix are highly heterogeneous, including multifractality of dimensions, e.g., cellular structures formed at different scales. Thus, to interrogate cellular heterogeneity and to obtain quantitative data about structural or DNA molecular morphological disorder (from the norm), it is generally necessary to establish a number of parameters. However, with the present IPR approach it is possible to selectively quantify structural changes in the nuclear DNA, by using DAPI stained confocal micrographs, and represent it in just one single parameter, namely the <IPR> value. The <IPR> value provides a measure of the degree of structural disorder, i.e., “disorder strength”, of the sample. Our preliminary results show an underlying relationship between structural disorder in nuclear DNA and carcinogenesis. Therefore, in this proposal, we will measure and quantify the submicron-scale structural disorder in the nuclear DNA of different normal and cancerous cells, obtained from cell cultures and tissues, via IPR analysis of the confocal micrographs. By coupling the IPR technique to the widely used confocal microscopy, we aim to (i) develop an automated quantification technique to measure the degree of structural disorder of selective molecular density in an organelle, in particular nuclear DNA, from DAPI stained confocal micrographs of the cells, and (ii) calibrate the degree of structural disorder in normal and cancer cells in liver, skin, and skeletal cell cultures and tissues nuclear structure. The success of this project will lead to a new direction in cancer detection, as well as cell characterization based on quantified structural changes in nuclear DNA.
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