Method for quantitative measurements of the elastic modulus of biological cells in AFM indentation experiments

Sokolov, Igor; Dokukin, Maxim; Guz, Nataliia

doi:10.1016/j.ymeth.2013.03.037

Cited by 149 publications

(155 citation statements)

References 96 publications

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“…These values are in accordance with a previously reported wet sample cell wall thickness (1.65 lm) measured at the interfacing area between two adjacent cells [58]. A difference between non-dried and rehydrated cell wall thicknesses was observed, which could be due to the inherent biological variability that is observed even among cells in the same tissue (Sokolov et al [59]; Zdunek and Pieczywek [60]) and/or due to changes in physical properties during the drying and rehydration process. An indepth analysis of these thickness changes is outside the scope of this study.…”

Section: Resultssupporting

confidence: 92%

The mechanical properties of plant cell walls soft material at the subcellular scale: the implications of water and of the intercellular boundaries

Zamil

Puri

2015

J Mater Sci

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Subcellular mechanical characterization of the cell wall can provide important insights into the cell wall's functional organization, especially if the characterization is not confounded by extracellular factors and intercellular boundaries. However, due to the technical challenges associated with the microscale mechanical characterization of soft biological materials, subcellular investigations of the plant cell wall under tensile loading have yet to be properly performed. This study reports the mechanical characterization of primary onion epidermal cell wall profiles using a novel cryosection-based sample preparation method and a microelectromechanical system-based tensile testing protocol. At the subcellular scale, the cell wall showed biphasic behavior similar to tissue samples. However, instead of a transition zone between the linear elastic or viscoelastic and linear plastic zones, the subcellular-scale samples showed a plateau-like trend with a sharp drop in the modulus value. The critical ranges of stress (20-40 MPa) and strain (5-12 %) of the plateau zone were identified. A strain energy of 1.3 MJ m -3 was calculated at the midpoint of the critical stress-strain range; this value was in accordance with the previously estimated hydrogen bond energy of the cell wall. Subcellular-scale samples showed very large lateral/axial deformations (0.8 ± 0.13) at fracturing. In addition, investigating the cell wall's mechanical properties at three different water states showed that water is critical for the flow-like behavior of cell wall matrix polymers. These results at subcellular scale provide new insights into biological materials that possess a structural hierarchy at different length scales; which cannot be obtained from tissue-scale experiments.

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Section: Resultssupporting

confidence: 92%

The mechanical properties of plant cell walls soft material at the subcellular scale: the implications of water and of the intercellular boundaries

Zamil

Puri

2015

J Mater Sci

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“…Results indicate that the average cell compression increases with time, that cells with fewer neighbors are more compressed than cells with larger numbers of neighbors, and that cell compression is relatively constant in the inner part of the colony and decays rapidly across the outer part of the colony. Biophysical Journal 109 (7) 1347-1357 bioPFC individual cells, which can be measured by atomic force microscopy probe indentation (see, e.g., Sokolov et al (41)), are much better known. To derive the Young's modulus of an individual cell from such indentation experiments, simple mechanical models are typically used (42).…”

Section: Discussionmentioning

confidence: 99%

A Mechanistic Collective Cell Model for Epithelial Colony Growth and Contact Inhibition

Aland

Hatzikirou

Lowengrub

et al. 2015

Biophysical Journal

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We present a mechanistic hybrid continuum-discrete model to simulate the dynamics of epithelial cell colonies. Collective cell dynamics are modeled using continuum equations that capture plastic, viscoelastic, and elastic deformations in the clusters while providing single-cell resolution. The continuum equations can be viewed as a coarse-grained version of previously developed discrete models that treat epithelial clusters as a two-dimensional network of vertices or stochastic interacting particles and follow the framework of dynamic density functional theory appropriately modified to account for cell size and shape variability. The discrete component of the model implements cell division and thus influences cell size and shape that couple to the continuum component. The model is validated against recent in vitro studies of epithelial cell colonies using Madin-Darby canine kidney cells. In good agreement with experiments, we find that mechanical interactions and constraints on the local expansion of cell size cause inhibition of cell motion and reductive cell division. This leads to successively smaller cells and a transition from exponential to quadratic growth of the colony that is associated with a constant-thickness rim of growing cells at the cluster edge, as well as the emergence of short-range ordering and solid-like behavior. A detailed analysis of the model reveals a scale invariance of the growth and provides insight into the generation of stresses and their influence on the dynamics of the colonies. Compared to previous models, our approach has several advantages: it is independent of dimension, it can be parameterized using classical elastic properties (Poisson's ratio and Young's modulus), and it can easily be extended to incorporate multiple cell types and general substrate geometries.

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“…This leads to several biomedical applications, such as regenerative medicine and tissue engineering 10,11 . Only recently 12,13 , several research groups devoted themselves finding a common methodology and protocol in order to validate, quantify, and ensure repeatability of results obtained in different laboratories, having led to the standardized nanomechanical AFM procedure (SNAP), introducing a methodology and relative corrections developed within a large network of laboratories 13 . While this is an important leap, the state-of-the-art methodology cannot overcome the intrinsic complexity of cells and biological world in general: strong heterogeneity from nanoscale to microscale (external and internal), morphological features, and natural time-dependent dynamics are raising challenges in experimental execution and particularly in data analysis.…”

Section: Introductionmentioning

confidence: 99%

Atomic force microscopy methodology and AFMech Suite software for nanomechanics on heterogeneous soft materials

et al. 2018

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Atomic force microscopy has proven to be a valuable technique to characterize the mechanical and morphological properties of heterogeneous soft materials such as biological specimens in liquid environment. Here we propose a 3-step method in order to investigate biological specimens where heterogeneity hinder a quantitative characterization: (1) precise AFM calibration, (2) nano-indentation in force volume mode, (3) array of finite element simulations built from AFM indentation events. We combine simulations to determine internal geometries, multi-layer material properties, and interfacial friction. In order to easily perform this analysis from raw AFM data to simulation comparison, we propose a standalone software, AFMech Suite comprising five interacting interfaces for simultaneous calibration, morphology, adhesion, mechanical, and simulation analysis. We test the methodology on soft hydrogels with hard spherical inclusions, as a soft-matter model system. Finally, we apply the method on E. coli bacteria supported on soft/hard hydrogels to prove usefulness in biological field.

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Method for quantitative measurements of the elastic modulus of biological cells in AFM indentation experiments

Cited by 149 publications

References 96 publications

The mechanical properties of plant cell walls soft material at the subcellular scale: the implications of water and of the intercellular boundaries

The mechanical properties of plant cell walls soft material at the subcellular scale: the implications of water and of the intercellular boundaries

A Mechanistic Collective Cell Model for Epithelial Colony Growth and Contact Inhibition

Atomic force microscopy methodology and AFMech Suite software for nanomechanics on heterogeneous soft materials

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