Cellular shear stiffness reflects progression of arsenic-induced transformation during G1

Abstract

Cancer cells consistently exhibit decreased stiffness; however, the onset and progression of this change have not been characterized. To study the development of cell stiffness changes, we evaluated the shear stiffness of populations of cells during transformation to a carcinogenic state. Bronchial epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage-independent growth. Shear stiffness of various cell populations in G1 was assessed using a novel non-invasive assay that applies shear stress with fluid flow and evaluates nanoscale deformation using quantitative phase imaging (QPI). Arsenic-treated cells exhibited reduced stiffness relative to control cells, while arsenic clonal lines, selected by growth in soft agar, were found to have reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation (RSD) of the stiffness of Arsenic clones was reduced compared with control clones, as well as to the arsenic-exposed cell population. Cell stiffness at the population level exhibits potential to be a novel and sensitive framework for identifying the development of cancerous cells.

Disorder strength measured by quantitative phase imaging as intrinsic cancer marker in fixed tissue biopsies

“…The results indicate that there are statistically significant differences between these two groups, therefore, the disorder strength can be utilized as a marker for a tissue screening. As demonstrated in [ 32 , 33 ], measurement of disorder strength can inform on the mechanical properties of a biological specimen and our results motivate further studies investigating how tissue mechanics vary with disease progression, with disorder strength used as a convenient metric.…”

“…Images obtained by SLIM has higher contrast than those obtained by other imaging systems, which result in higher phase variance. In addition, tissue biopsy cores generally have a complex structures compared with single cells which were used in the previous works [ 32 , 33 ]. Fig 5 shows the averaged disorder strength across the tissue area.…”

“…Furthermore, A. Muñoz et al . evaluated the shear stiffness of populations of cells during transformation to a carcinogenic state using a QPI-based method and applied it to identify the development of cancerous cells [ 33 ].…”

Tissue spatial correlation as cancer marker

“…They applied this analysis to colon, skin, and lung cancer cells to demonstrate an inverse relationship between shear stiffness and disorder strength. Building on these results, Muñoz et al 38 used QPI to study the on-set and progression of shear stiffness changes during malignant transformation in bronchial epithelial cells. Our group also showed that the disorder strength measured by spatial light interference microscopy (SLIM), a sensitive white light QPI method, is a quantitative marker of malignancy that can be used to classify benign and malignant breast tissue microarray (TMA) cores.…”

Tissue spatial correlation as cancer marker

“…Building on these results, A. Muoz et al used QPI to study the on-set and progression of shear stiffness changes during malignant transformation in bronchial epithelial cells. 38 Our group also showed that the disorder strength measured by spatial light interference microscopy (SLIM), a sensitive white light QPI method, is a quantitative marker of malignancy that can be used to classify benign and malignant breast tissue microarray (TMA) cores. 8 In this paper, we propose the local spatial autocorrelation length as a new intrinsic marker of nanoscale morphological alteration in fixed tissue biopsies.…”