Quantitative mechanical analysis of indentations on layered, soft elastic materials

Doss, Bryant L.; Eliato, Kiarash Rahmani; Lin, Keng Hui; Ros, Robert

doi:10.1039/c8sm02121j

Cited by 28 publications

(49 citation statements)

References 38 publications

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“…Bottom-effect correction models have been validated by using finite element model simulations on elastic materials. 31,32 However, an earlier bottom-effect correction model developed for a conical tip acting on an elastic material 30 fails to agree with the simulations and other models. 31,32 Living cells show a variety of viscoelastic phenomena which remain insufficiently understood.…”

Section: Introductionmentioning

confidence: 83%

“…The combination of the cell's softness, its finite-thickness and the rigidity of solid support has given rise to the bottomeffect artefact during the acquisition of a FDC. [29][30][31][32] This artefact makes cells to appear stiffer than they are. This effect, if it is not corrected, introduces significant quantitative errors in the determination of the Young's modulus of a cell.…”

Section: Introductionmentioning

confidence: 99%

“…31 Ros and co-workers have developed an approximate bottom-effect correction for the determination of the Young's modulus that is valid for rigid and soft supports. 32 A bottom-effect correction theory gives the force as a series of terms that depend on the indentation, contact area and cell's thickness. Bottom-effect correction models have been validated by using finite element model simulations on elastic materials.…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2020

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“…Furthermore, it demands the indentation depth to be small compared to the diameter of the ball and no hysteresis side-effects should occur. The maximum indentation depth was less than 2% of the sample thickness, therefore Bueckle's indentation depth limit of 10% of the sample thickness was not exceeded (32,33,39). See paragraph "Application of the Hertz model" below for a test and discussion of the other assumptions.…”

Section: Data Analysis and Elastic Modulus Calculationmentioning

confidence: 97%

“…0.3 to 2% of the sample thickness. The indentation depth was chosen to be small compared to the sample thickness (32,33). Force data was analysed in Igor Pro (Wave Metrics, USA) using custom-written software applying the Hertzian contact model (see Note S4).…”

Section: Nanomechanical Characterizationmentioning

confidence: 99%

Proof-of-concept for the detection of early osteoarthritis pathology by endomicroscopy

Tschaikowsky

Brander

Balzer

et al. 2019

Preprint

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†shared last authorship. One Sentence Summary:We report a correlation between articular cartilage surface nanoscale stiffness and chondrocyte spatial organization; using this correlation enables early pathology detection by currently available clinical optical methods. Abstract:Osteoarthritis (OA) is a degenerative joint disease and the leading cause of global disability.Clinical trials to date have been unable to pinpoint early and potentially reversible disease states with current clinical technology and hence disease-modifying OA drug candidates cannot be tested early in the disease. To overcome this obstacle, we correlate articular cartilage stiffness changes and cellular spatial organization. The former is a well-understood and functionally relevant OA pathology, while the latter allows discriminating between healthy vs early OA, based on distinct cellular spatial patterns. We demonstrated that an extensive loss of atomic force microscopydetected stiffness can be seen in cartilage tissues with spatial patterns exhibiting the earliest identifiable OA. In addition, the translation of commercially available clinically usable probebased confocal laser-endomicroscopy allows us to detect these early OA spatial patterns. This study resolves a major clinical trial obstacle by presenting the proof-of-concept that early OA pathology can be detected by already available clinical technology.

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Bottom Effect in Atomic Force Microscopy Nanomechanics

Chiodini

Ruiz-Rincón

García

et al. 2020

Small

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In this work, the influence of the rigid substrate on the determination of the sample Young's modulus, the so‐called bottom‐effect artifact, is demonstrated by an atomic force microscopy force‐spectroscopy experiment. The nanomechanical properties of a one‐component supported lipid membrane (SLM) exhibiting areas of two different thicknesses are studied: While a standard contact mechanics model (Sneddon) provides two different elastic moduli for these two morphologies, it is shown that Garcia's bottom‐effect artifact correction yields a unique value, as expected for an intrinsic material property. Remarkably, it is demonstrated that the ratio between the contact radius (and not only the indentation) and the sample thickness is the key parameter addressing the relevance of the bottom‐effect artifact. The experimental results are validated by finite element method simulations providing a solid support to Garcia's theory. The amphiphilic nature of the investigated material is representative of several kinds of lipids, suggesting that the results have far reaching implications for determining the correct Young's modulus of SLMs. The generality of Garcia's bottom‐effect artifact correction allows its application to every kind of supported soft film.

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Quantitative mechanical analysis of indentations on layered, soft elastic materials

Cited by 28 publications

References 38 publications

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

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

Proof-of-concept for the detection of early osteoarthritis pathology by endomicroscopy

Bottom Effect in Atomic Force Microscopy Nanomechanics

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