Biophysical properties of human breast cancer cells measured using silicon MEMS resonators and atomic force microscopy

Abstract

Biophysical studies on individual cells can help to establish the relationship between mechanics and biological function. In the case of cancer, mechanical properties of cells have been linked to metastatic activity and disease progression and can be crucial for understanding cellular physiology and metabolism. In this study, we report measurements of the stiffness of breast cancer cells using a novel silicon MEMS resonant sensor and validated the results with atomic force microscopy (AFM). We measured the mass and stiffness of individual benign (MCF-10A), non-invasive malignant (MCF-7), and highly-invasive malignant (MDA-MB-231) breast cancer cells using the silicon resonant MEMS sensors. The sensor extracts the average stiffness value of the whole cell and allows comparison of stiffness of different cell types. We found differences between the cell lines in both elasticity and viscosity, and confirmed our observations through independent measurements with atomic force microscopy (AFM). Coupled with measurements over time, this approach could lead to a multimodal investigation of both growth and physical properties of single cells. The mechanical property sensitivity and resolution of these pedestal sensors were investigated to understand the significance of the frequency shift during operation. The lowest achievable spring constant and damping constant resolutions have a range of 0.06 to 17.10 mN m(-1) and 1.63 to 1.96 nN s m(-1), respectively, measured across the range of physiological cell mechanical properties.

Simultaneous Measurement of Multiple Mechanical Properties of Single Cells Using AFM by Indentation and Vibration

“…4(c) with left vertical axis). Therefore, living cells are much softer than fixed cells, and the stiffness of living cells is only 42.46% that of fixed cells, which is consistent with previous reports results [8], [24], [34], [38], [43]- [46]. According to the cellular AFM image [see Fig.…”

“…According to (5), the resonance frequency (ω 0 ) of a sample cell is proportional to k and inversely proportional to m; therefore, the calculated ω 0 of a fixed cell is larger than that of a living cell. Furthermore, fixed cells have higher viscosities relative to living cells (p < 0.05; 0.700 μN s m -1 for fixed cells, and 0.393 μN s m -1 for living cells), as reported previously [12], [24], [37]. The comprehensive mechanical properties of living (blue star) and fixed (red star) sample cells acquired at the vibration frequency of 0.3 kHz are presented in Fig.…”

“…According to the measurement of AFM indentation experiment and the reports about the cellular mechanical properties measurement [8], [24], [37], the mechanical parameters m, k and c were defined to be low mass and viscoelasticity. The mass parameter m was fixed at 5 ng, and the frequency ω was varied within 10 kHz, with k ranging from 0.05 to 0.5 N/m to fix the mechanical property c = 10 μN s m -1 and with c ranging from 10 to 200 μN s m -1 to fix the mechanical property k = 0.05 N/m.…”

“…Furthermore, an array of micro-electro-mechanical system (MEMS) resonant sensors combined with a laser Doppler vibrometer (LDV) can be utilized to measure the micromechanical properties of bio-samples and hydrogels, including their mass and viscoelasticity parameters, based on various vibration quantities, such as resonance frequency shifts, vibrationinduced phase shifts and amplitude ratios [8], [12], [21]- [24]. However, using QCM, QCM-D and resonant sensors requires that the biological samples be adhered onto measuring platforms that must be sterilized and functionalized with collagen for biocompatibility.…”

“…A second-order mass-spring-damper harmonic oscillator system was used to model the dynamical forced vibration of a sample cell actuated by the substrate vibration, under the assumption that the cell was composed of homogeneous, isotropic and linearly elastic material [24], [32]. The thickness-corrected Hertz model was adopted to calculate the cellular Young's modulus based on the indentation force curves [33], which is converted to the elasticity parameter (k) for further computation of the mass (m) and viscous damper parameter (c) of the mass-spring-damper harmonic model of a cell.…”