Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer.
Cells contributing to the pathogenesis of cancer possess cytoplasmic and nuclear structural alterations that accompany their aberrant genetic, epigenetic, and molecular perturbations. Although it is known that architectural changes in primary and metastatic tumor cells can be quantified through variations in cellular density at the nanometer and micrometer spatial scales, the interdependent relationships among nuclear and cytoplasmic density as a function of tumorigenic potential has not been thoroughly investigated. We present a combined optical approach utilizing quantitative phase microscopy and partial wave spectroscopic microscopy to perform parallel structural characterizations of cellular architecture. Using the isogenic SW480 and SW620 cell lines as a model of pre and postmetastatic transition in colorectal cancer, we demonstrate that nuclear and cytoplasmic nanoscale disorder, micron-scale dry mass content, mean dry mass density, and shape metrics of the dry mass density histogram are uniquely correlated within and across different cellular compartments for a given cell type. The correlations of these physical parameters can be interpreted as networks whose nodal importance and level of connection independence differ according to disease stage. This work demonstrates how optically derived biophysical parameters are linked within and across different cellular compartments during the architectural orchestration of the metastatic phenotype.
Northwestern University, Biomedical Engineering Department, Evanston, Illinois 60208.
Dhwanil
D
Damania
Northwestern University, Biomedical Engineering Department, Evanston, Illinois 60208.
Hariharan
H
Subramanian
Northwestern University, Biomedical Engineering Department, Evanston, Illinois 60208.
Vadim
V
Backman
Oregon Health & Science University, Knight Cancer Institute, Portland, Oregon 97239.
Eric C
EC
Anderson
Oregon Health & Science University, Knight Cancer Institute, Portland, Oregon 97239cOregon Health & Science University, School of Medicine, Department of Cell & Developmental Biology, Portland, Oregon 97239dOregon Health & Science University, School of Me.
Melissa H
MH
Wong
Oregon Health & Science University, Knight Cancer Institute, Portland, Oregon 97239cOregon Health & Science University, School of Medicine, Department of Cell & Developmental Biology, Portland, Oregon 97239eOregon Health & Science University, School of Me.
Owen J T
OJ
McCarty
Oregon Health & Science University, School of Medicine, Department of Dermatology, Portland, Oregon 97239eOregon Health & Science University, School of Medicine, Department of Biomedical Engineering, Portland, Oregon 97239.
Kevin G
KG
Phillips
D055592:Biophysical Phenomena; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D008207:Lymphatic Metastasis; D008853:Microscopy / Q000379:methods; D009362:Neoplasm Metastasis; D055095:Optics and Photonics; D010641:Phenotype; D013053:Spectrophotometry