Research Mentor Name

Jitao Zhang

Research Mentor Email Address

zhan2399@msu.edu

Institution / Department

Wayne State University Department of Biomedical Engineering

Document Type

Research Abstract

Research Type

basicbio

Graduate Level Research

no

Abstract

Background: Breast cancer progression and metastasis are closely linked to alterations in the mechanical properties of tumor cells and their microenvironment. Softer, more deformable cells are often associated with higher metastatic potential. While atomic force microscopy (AFM) is the current gold standard for mechanical characterization, it is limited to surface measurements and can damage 3D cultures. It remains unclear how the mechanical properties evolve over time in normal versus malignant spheroids. This study utilizes Brillouin light-scattering microscopy, a non-contact and label-free optical technique, to assess stiffness changes in normal and malignant breast epithelial spheroids over time. Understanding these mechanical signatures can provide insight into tumor invasion dynamics and may inform strategies for early detection and treatment assessment.

Methods: Five normal breast epithelial (MCF10A; M1) and ten malignant breast tumor (MCF10CA1h; M3) spheroids were cultured in 3D Matrigel and imaged on days 2, 5, and 8 using a confocal Brillouin microscope (660 nm laser, 20 mW, 40× objective). Brillouin frequency spectra were acquired and analyzed in MATLAB to extract the Brillouin shift (Ωᴮ) at each voxel (volumetric pixel). Assuming the refractive index and density remained constant across groups, Ωᴮ was interpreted as a relative measure of stiffness. Statistical comparisons were performed using Welch’s unpaired t-test.

Results: Brillouin microscopy revealed distinct stiffness dynamics between normal and malignant spheroids. Both M1 and M3 spheroids increased in size from day 2 to day 8, but M1 consistently exhibited a larger average diameter. M1 spheroids showed a continuous increase in average Brillouin shift from 0.222 to 0.288 GHz, indicating progressive stiffening with growth. M3 spheroids increased from 0.215 GHz to 0.256 GHz by day 5, followed by a decrease to 0.223 GHz by day 8, suggesting late-stage softening and increased deformability. On all days, M1 spheroids were stiffer than M3, with the difference reaching statistical significance on day 8 (p < 0.001). Increasing standard deviation across both groups indicated greater internal mechanical heterogeneity as spheroids matured.

Conclusion: Brillouin microscopy detected temporal and cell-type-specific differences in spheroid stiffness. The late-stage softening of malignant spheroids supports the inverse relationship between stiffness and metastatic potential. These findings demonstrate the feasibility of Brillouin microscopy as a non-invasive technique for observing the evolution of tumor biomechanics and suggest that mechanical properties may serve as emerging biomarkers for cancer aggressiveness.

Disciplines

Atomic, Molecular and Optical Physics | Bioimaging and Biomedical Optics | Biological Engineering | Biomechanics and Biotransport | Biomedical Devices and Instrumentation | Biomedical Engineering and Bioengineering | Medicine and Health Sciences | Optics

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