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      A comparison of methods to assess cell mechanical properties

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          Abstract

          <p class="first" id="P1">Cell mechanics controls important cellular and subcellular functions, including cell adhesion, migration, polarization, and differentiation, as well as organelle organization, and trafficking inside the cytoplasm. Yet, reported values of cell stiffness and viscosity vary strongly, suggesting disagreements in how results of different methods are obtained or analyzed. To address this issue and illustrate the complementarity of different instruments, we present, analyze, and critically compare measurements conducted by some of the most widely used methods of cell mechanics: atomic force microscopy, magnetic twisting cytometry, particle-tracking microrheology, parallel-plates rheometry, cell monolayer rheology, and the optical stretcher. These measurements highlight that elastic and viscous moduli of MCF-7 breast cancer cells can vary 1,000 fold and 100 fold, respectively. We discuss the sources of these variations, including the level of applied mechanical stress and rate of deformation, the geometry of the probe, the location probed in the cell, and the extracellular microenvironment. </p>

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          Most cited references45

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          The optical stretcher: a novel laser tool to micromanipulate cells.

          When a dielectric object is placed between two opposed, nonfocused laser beams, the total force acting on the object is zero but the surface forces are additive, thus leading to a stretching of the object along the axis of the beams. Using this principle, we have constructed a device, called an optical stretcher, that can be used to measure the viscoelastic properties of dielectric materials, including biologic materials such as cells, with the sensitivity necessary to distinguish even between different individual cytoskeletal phenotypes. We have successfully used the optical stretcher to deform human erythrocytes and mouse fibroblasts. In the optical stretcher, no focusing is required, thus radiation damage is minimized and the surface forces are not limited by the light power. The magnitude of the deforming forces in the optical stretcher thus bridges the gap between optical tweezers and atomic force microscopy for the study of biologic materials.
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            Particle-tracking microrheology of living cells: principles and applications.

            A multitude of cellular and subcellular processes depend critically on the mechanical deformability of the cytoplasm. We have recently introduced the method of particle-tracking microrheology, which measures the viscoelastic properties of the cytoplasm locally and with high spatiotemporal resolution. Here we establish the basic principles of particle-tracking microrheology, describing the advantages of this approach over more conventional approaches to cell mechanics. We present basic concepts of molecular mechanics and polymer physics relevant to the microrheological response of cells. Particle-tracking microrheology can probe the mechanical properties of live cells in experimentally difficult, yet more physiological, environments, including cells embedded inside a 3D matrix, adherent cells subjected to shear flows, and cells inside a developing embryo. Particle-tracking microrheology can readily reveal the lost ability of diseased cells to resist shear forces.
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              The cytoplasm of living cells behaves as a poroelastic material

              The cytoplasm is the largest part of the cell by volume and hence its rheology sets the rate at which cellular shape changes can occur. Recent experimental evidence suggests that cytoplasmic rheology can be described by a poroelastic model, in which the cytoplasm is treated as a biphasic material consisting of a porous elastic solid meshwork (cytoskeleton, organelles, macromolecules) bathed in an interstitial fluid (cytosol). In this picture, the rate of cellular deformation is limited by the rate at which intracellular water can redistribute within the cytoplasm. However, direct supporting evidence for the model is lacking. Here we directly validate the poroelastic model to explain cellular rheology at physiologically relevant timescales using microindentation tests in conjunction with mechanical, chemical and genetic treatments. Our results show that water redistribution through the solid phase of the cytoplasm (cytoskeleton and macromolecular crowders) plays a fundamental role in setting cellular rheology.
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                Author and article information

                Journal
                Nature Methods
                Nat Methods
                Springer Nature
                1548-7091
                1548-7105
                June 18 2018
                Article
                10.1038/s41592-018-0015-1
                6582221
                29915189
                a9d1ad2c-dceb-41e7-9b1f-1bd172978181
                © 2018

                http://www.springer.com/tdm

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