Evaluation of nonlinear dynamics of the cell structure damage as a promising method for personalized cancer diagnostics

Abstract

Background: Modulation interference microscopy is one of the promising technologies for early personalized cancer diagnostics, while it gives the possibility to obtain real-time images of living functioning cells at a nanometer resolution, as well as to assess spatio-temporal changes of their intracellular structures.Aim: To identify the markers of malignant transformation of cells based on a multiple scale spatio-temporal of the data obtained by lase interferometry during in situ registration of changes in intracellular structures.Materials and methods: The study was performed with the breast adenocarcinoma MCF-7 cell line and human kidney epithelial cells HEK 293 provided by the N.N. Blokhin National Medical Research Centre of Oncology (Moscow, Russia). Changes in fluctuation of the living cell phase thickness were measured with a laser modulation interference microscope MIM-340 (PA UOMZ, Russia). The multifractal detrended fluctuation analysis (MF-DFA) was used to assess the results obtained.Results: By comparison of the scaling exponential spectra and corresponding spectra of the singular fluctuations in the minimal and maximal diameters of the phase pictures of HEK 293 cells and MCF-7 cells, it was shown that the cancer cell dynamics has definite monofractal properties: a linear dependency of the scaling exponents τ from the actual q parameter and “dotted” singularity spectrum (the spectral width does not exceed 0.1). The dynamics of healthy cell demonstrated multifractal properties, such as a non-linear dependency τ(q) and a bell shaped singularity spectrum (the spectral width over 0.1).Conclusion: We have proposed a new approach to assess the intracellular structural damage during oncogenesis. The signs of monofractality are objective criteria of malignization. The results obtained seems promising as early diagnostic markers of cancer transformation (damage) of cells and determination of tumor cell sensitivity / resistance to anti-tumor agents in an individual patient.

Keywords

• laser interference microscopy
• mcf-7 breast adenocarcinoma cells
• human kidney epithelial cells hek 293
• spatio-temporal invariants
• cancer cell damage