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Valproic Acid Treatment Enhances Chromosome Flexibility and Electron Transport in MCF7 Breast Cancer Cells

Agrawal, T.; PAUL, D.; Mishra, A.; Ganesan, A. K.; Pal, S.; Rakshit, T.

2024-04-11 biophysics
10.1101/2024.04.08.588551 bioRxiv
Show abstract

The structural integrity of the chromosomes is essential to every functional process within the eukaryotic nuclei. Chromosomes are DNA-histone complexes essential for the inheritance of genetic information to the offspring and any defect in it is linked to mitotic errors, cancer growth, and cellular aging. Changes in the mechanical properties of a chromosome could lead to its compromised function and stability, leading to chromosome breaks. Here, we studied the changes in chromosome physical properties using metaphase chromosomes isolated from human breast cancer cells (MCF7) exposed to Valproic Acid (VPA), a known epigenetic modifier drug involved in histone hyperacetylation and DNA demethylation. Due to chromosomal structural intricacy, preparative and technical limitations of analytical tools, we employed a label-free atomic force microscopy approach for simultaneously visualizing and mapping single chromosome elasticity. Additionally, we performed electron transport characteristics of metaphase chromosomes to elucidate the effect of VPA. Our multi-parametric strategy of probing physical properties of chromosomes offers a new scope in terms of analytical tools for studying chromosomal structural changes/aberrations and associated structure-function relationships pertinent to cancer.

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