Quantification of nanoscale density fluctuations by electron microscopy: Probing cellular alterations in early carcinogenesis

Prabhakar Pradhan*, Dhwanil Damania, Hrushikesh M. Joshi, Vladimir Turzhitsky, Hariharan Subramanian, Hemant K. Roy, Allen Taflove, Vinayak P. Dravid, Vadim Backman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed.

Original languageEnglish (US)
Article number026012
JournalPhysical Biology
Volume8
Issue number2
DOIs
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology
  • Cell Biology

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