Abstract
Countless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease. Here, an iterative-fitting methodology visualizes the time-dependent viscoelastic behavior of human skin cells under physiologically relevant conditions. Past investigations often involved parameterizing elastic relationships and assuming purely Hertzian contact mechanics, which fails to properly account for the rich temporal information available. We demonstrate the performance superiority of the proposed iterative viscoelastic characterization method over standard open-search approaches. Our viscoelastic measurements revealed that 2D adherent metastatic melanoma cells exhibit reduced elasticity compared to their normal counterparts—melanocytes and fibroblasts, and are significantly less viscous than fibroblasts over timescales spanning three orders of magnitude. The measured loss angle indicates clear differential viscoelastic responses across multiple timescales between the measured cells. This method provides insight into the complex viscoelastic behavior of metastatic melanoma cells relevant to better understanding cancer metastasis and aggression.
Highlights
Countless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease
All cell types exhibited their strongest viscous action near 10 kHz (Fig. 4b), and mostly displayed decreasing viscous action below and above those frequencies, with the melanoma and fibroblast datasets showing larger loss moduli than melanocytes. These observations suggest that analysis of the frequency-dependent viscoelastic behavior of human skin cells could be used to unambiguously differentiate cancerous cells from their normal counterparts
In regard to deep indentations, the Lee and Radok viscoelastic framework is defined for relatively small strains; a recent computational study found that classical contact mechanics models are robust with higher indentations yielding errors less than 5%47
Summary
Countless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease. The measured loss angle indicates clear differential viscoelastic responses across multiple timescales between the measured cells This method provides insight into the complex viscoelastic behavior of metastatic melanoma cells relevant to better understanding cancer metastasis and aggression. Characterizing the mechanical response that occurs over short timescales (at seconds timescales) could provide significant insight into individual cellular processes, such as filamentous actin cortex cytoskeleton remodeling[39], turnover of actin filament crosslinkers[40], myosin motor fast contractility[41], microtubule assembly or disassembly[42], and vesicle trafficking[43] to name several These single-cell biological processes are essential for cellular tissue functions including cell and tissue homeostasis, development, and disease progression including cancer metastasis. The study provides a general understanding of the complex viscoelastic behavior of living metastatic melanoma, which is relevant to better understanding metastasis and aggression
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