Role of Cytoskeleton in Controlling the Disorder Strength of Cellular Nanoscale Architecture

Abstract

Cytoskeleton is ubiquitous throughout the cell and is involved in important cellular processes such as cellular transport, signal transduction, gene transcription, cell-division, etc. Partial wave spectroscopic microscopy is a novel optical technique that measures the statistical properties of cell nanoscale organization in terms of the disorder strength. It has been found previously that the increase in the disorder strength of cell nanoarchitecture is one of the earliest events in carcinogenesis. In this study, we investigate the cellular components responsible for the differential disorder strength between two morphologically (and hence microscopically) similar but genetically altered human colon cancer cell lines, HT29 cells and Csk shRNA-transfected HT29 cells that exhibit different degrees of neoplastic aggressiveness. To understand the role of cytoskeleton in nanoarchitectural alterations, we performed selective drug treatment on the specific cytoskeletal components of these cell types and studied the effects of cytoskeletal organization on disorder strength differences. We report that altering the cell nanoarchitecture by disrupting cytoskeletal organization leads to the attenuation of the disorder strength differences between microscopically indistinguishable HT29 and CSK constructs. We therefore demonstrate that cytoskeleton plays a role in the control of cellular nanoscale disorder.

MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression

“…It has been shown that there is a strong correlation between the strength of the local morphological distortion ( L md ) in nuclear chromatin structure and the cancer stage, both increase with the progression of carcinogenesis 16 . Therefore, quantification of the strength of the morphological distortion provides the stage or degree of aggressiveness of the cancer in a biological cell.…”

“…The increased nanoscale architectural changes in tumor tissues displaying MUC13 and HER2 interaction depict increased aggressiveness and malignant properties of the tumor 16, 18, 20 . These studies do not provide definitive information about the evaluation of disorder strength due to interaction of MUC13 with HER2.…”

Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

“…1(b)] were carried out on a second-generation instrument described in detail elsewhere. 36 Briefly, a plane wave of white light from a xenon lamp (150 W; Oriel, Stratford, CT) is produced by a 4f-lens relay system that focuses onto the sample plane by a low NA ¼ 0.2 condenser lens. Light reflected by the specimen is collected by a NA ¼ 0.4 objective lens (Edmund Optics, Barrington, NJ).…”

Reconstruction of explicit structural properties at the nanoscale via spectroscopic microscopy

“…After confirming with AFM that the necessary condition for our algorithm accuracy-precise knowledge of cell thickness-has been satisfied, we measured the intracellular σ n Δ and l c of two genetic variants of human adenocarcinoma HT29 cell lines. Due to their columnar epithelial cell type, 85% to 90% of the measured cell volume 30 was occupied by the cell nucleus, and thus the measured structure was predominantly determined by the nuclear organization of these cells. Results of our analysis showed that while both variants of HT29 cells have a similar RI spatial correlation length l c , the standard deviation of RI within the CV exceeded that in the EGFR-knockdown variant by a factor of 2.…”