Mapping power-law rheology of living cells using multi-frequency force modulation atomic force microscopy

Takahashi, Ryōsuke; Okajima, Takaharu

doi:10.1063/1.4934874

Cited by 40 publications

(28 citation statements)

References 31 publications

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“…35 Nonetheless, we note that AFMoscillatory microrheology experiments report the existence of several viscoelastic regimes with different power-law exponents. 40,61 In addition, experiments performed with other microrheology methods have also reported the existence of several power-law exponents. 62…”

Section: Nanorheology Of Living Cells From Force-distance Curvesmentioning

confidence: 99%

Nanorheology of living cells measured by AFM-based force–distance curves

2020

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Mechanobiology aims to establish functional relationships between the mechanical state of a living a cell and its physiology. The acquisition of force-distance curves with an AFM is by far the dominant method to characterize the nanomechanical properties of living cells. However, theoretical simulations have shown that the contact mechanics models used to determine the Young's modulus from a force-distance curve could be off by a factor 5 from its expected value. The semi-quantitative character arises from the lack of a theory that integrates the AFM data, a realistic viscoelastic model of a cell and its finitethickness. Here, we develop a method to determine the mechanical response of a cell from a force-distance curve. The method incorporates bottom-effect corrections, a power-law rheology model and the deformation history of the cell. It transforms the experimental data into viscoelastic parameters of the cell as a function of the indentation frequency. The quantitative agreement obtained between the experiments performed on living fibroblast cells and the analytical theory supports the use of force-distance curves to measure the nanorheological properties of cells. † Electronic supplementary information (ESI) available: Complete derivation of the analytical expressions for PLR and KV models, coefficients for a conical tip, correspondence between velocities and equivalent indentation frequencies, statistical analysis of the experiments performed on NIH 3T3 fibroblasts. See

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Section: Nanorheology Of Living Cells From Force-distance Curvesmentioning

confidence: 99%

Nanorheology of living cells measured by AFM-based force–distance curves

2020

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“…S2)26. Measurements were carried out in the perinuclear region to reduce variability and minimize bottom effects27, 28, 29, and at indentations ≲300 nm and with an oscillation amplitude of 15 nm, thus probing mainly the cortical cytoskeleton30. Up to 300 Hz, both moduli increased with frequency at a similar rate, as shown by the increased slope and hysteresis of the force-indentation cycles (Fig 1E) with G’ ( f )> G” ( f ) and average loss tangent η ~0.25 (Fig.…”

mentioning

confidence: 99%

High-frequency microrheology reveals cytoskeleton dynamics in living cells

et al. 2017

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Living cells are viscoelastic materials, with the elastic response dominating at long timescales (≳1 ms)1. At shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce2. Here, we develop high-frequency microrheology (HF-MR) to probe the viscoelastic response of living cells from 1Hz to 100 kHz. We report the viscoelasticity of different cell types and upon cytoskeletal drug treatments. At previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequency, providing a univocal mechanical fingerprint. Microrheology over a wide dynamic range up to the frequency of action of the molecular components provides a mechanistic understanding of cell mechanics.

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“…This narrow range of loss tangent is consistent with the conserved ratio of cortical tension to cell viscosity in leukocytes (see introduction). In biological matter, similar to soft glassy materials 60,61 , stress relaxation over time often follows a power-law (with an exponent that we shall call ) 43,[45][46][47][48] . The loss tangent as defined by the ratio of loss and storage moduli is frequency-dependent, but is expected to be approximately equal to tan ( 2 ) at low frequencies (Suppl.…”

Section: Relationship Between Elastic and Viscous Properties During Lmentioning

confidence: 99%

“…Cellular matter is indeed particular in that elastic and viscous properties of cells are usually not independent: resting leukocytes such as neutrophils 41,42 and macrophages 6 conserve a ratio of cortical tension to cell viscosity of about 0.2-0.3 µm/s, even though macrophages can be ten times more tense than neutrophils. Many studies showed this peculiar aspect of biological matter in other cell types 20,[43][44][45][46][47][48] . What remained unknown was whether this link between elastic and viscous properties would be conserved over time even during mechanical changes due to cell function, e.g.…”

Section: Introductionmentioning

confidence: 97%

Single-cell immuno-mechanics: rapid viscoelastic changes are a hall-mark of early leukocyte activation

Zak

Cortés

Sadoun

et al. 2019

Preprint

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143 words/150) To accomplish their critical task of removing infected cells and fighting pathogens, leukocytes activate by forming specialized interfaces with other cells. Using an innovative micropipette rheometer, we show in three different cell types that when stimulated by microbeads mimicking target cells, leukocytes become up to ten times stiffer and more viscous. These mechanical changes initiate within seconds after contact and evolve rapidly over minutes. Remarkably, leukocyte elastic and viscous properties evolve in parallel, preserving a well-defined ratio that constitutes a mechanical signature specific to each cell type. The current results indicate that simultaneously tracking both elastic and viscous properties during an active cell process provides a new way to investigate cell mechanical processes. Our findings also suggest that dynamic immuno-mechanical measurements provide an identifier of leukocyte type and an indicator of the cell's state of activation.

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Mapping power-law rheology of living cells using multi-frequency force modulation atomic force microscopy

Cited by 40 publications

References 31 publications

Nanorheology of living cells measured by AFM-based force–distance curves

Nanorheology of living cells measured by AFM-based force–distance curves

High-frequency microrheology reveals cytoskeleton dynamics in living cells

Single-cell immuno-mechanics: rapid viscoelastic changes are a hall-mark of early leukocyte activation

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