Standardized microgel beads as elastic cell mechanical probes

Girardo, Salvatore; Träber, Nicole; Wagner, Katrin; Cojoc, Gheorghe; Herold, C.; Goswami, Ruchi; Schlüßler, Raimund; Abuhattum, Shada; Taubenberger, Anna; Reichel, Felix; Mokbel, Dominic; Herbig, Maik; Schürmann, Mirjam; Müller, Paul; Heida, Thomas; Jacobi, Angela; Ulbricht, Elke; Thiele, Julian; Werner, Carsten; Guck, Jochen

doi:10.1039/c8tb01421c

Cited by 91 publications

(130 citation statements)

References 93 publications

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“…Young's elastic modulus is commonly used for specifying a cell's time‐independent mechanical properties . To directly correlate the maximum streaming velocity to the Young's modulus of cells under the same experimental conditions, we use atomic force microscopy (AFM) .…”

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confidence: 99%

Dancing with the Cells: Acoustic Microflows Generated by Oscillating Cells

Salari

Appak-Baskoy

Ezzo

et al. 2019

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The interaction of a sound or ultrasound wave with an elastic object, such as a microbubble, can give rise to a steady‐state microstreaming flow in its surrounding liquid. Many microfluidic strategies for cell and particle manipulation, and analyte mixing, are based on this type of flow. In addition, there are reports that acoustic streaming can be generated in biological systems, for instance, in a mammalian inner ear. Here, new observations are reported that individual cells are able to induce microstreaming flow, when they are excited by controlled acoustic waves in vitro. Single adherent cells are exposed to an acoustic field inside a microfluidic device. The cell‐induced microstreaming is then investigated by monitoring flow tracers around the cell, while the structure and extracellular environment of the cell are altered using different chemicals. The observations suggest that the maximum streaming flow induced by an MDA‐MB‐231 breast cancer cell can reach velocities on the order of mm s−1, and this maximum velocity is primarily governed by the overall cell stiffness. Therefore, such cell‐induced microstreaming measurements, including flow pattern and velocity magnitude, may be used as label‐free proxies of cellular mechanical properties, such as stiffness.

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confidence: 99%

Dancing with the Cells: Acoustic Microflows Generated by Oscillating Cells

Salari

Appak-Baskoy

Ezzo

et al. 2019

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“…Recent reports have described deformable hydrogel particles that can be used as passive force sensors in multicellular aggregates and tissues 15,16 . Compared to the single microfluidic channel methods chosen previously, our batch particle synthesis method is simpler, and requires little specialized expertise or facilities.…”

Section: Live-cell Force Dynamics Within the Cytotoxic T Cell Immunolmentioning

confidence: 99%

“…5). Indentation curves (or force deformation curves, FDCs) were first processed by correction for drift in the baseline and to be incompressible (Poisson ratio = 0.5), which was previously shown to be a good approximation for bulk 39 and microparticle 16 acrylamide gels. Furthermore, the indentation-induced deformation was assumed to only deform the upper part of the DAAM-particles, which is in contact with the AFM tip.…”

Section: Atomic Force Microscopy Measurementsmentioning

confidence: 99%

“…However, current technologies have lacked the resolution to identify individual subcellular force transmitting structures. Moreover, synthesis of suitable hydrogel MPs for such applications can be rather complex, often requiring specialized expertise in microfluidics 15,16 . Particle properties, especially their size and mechanical properties, must also be optimized for accurate traction measurements 16 .…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, synthesis of suitable hydrogel MPs for such applications can be rather complex, often requiring specialized expertise in microfluidics 15,16 . Particle properties, especially their size and mechanical properties, must also be optimized for accurate traction measurements 16 . Finally, deformable microparticles have so far only been used as passive force reporters without biologically specific ligands, despite the fact that MPs can be chemically modified to trigger and elicit specific cellular behaviors.…”

Section: Introductionmentioning

confidence: 99%

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Superresolved microparticle traction force microscopy reveals subcellular force patterns in immune cell-target interactions

Vorselen

Wang²,

et al. 2018

Preprint

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Force exertion is an integral part of cellular behavior. Traction force microscopy (TFM) has been instrumental for studying such forces, providing both spatial and directional force measurements at subcellular resolution. However, the applications of classical TFM are restricted by the typical planar geometry. Here, we develop a particle-based force sensing strategy, specifically designed for studying ligand-dependent cellular interactions. We establish a straightforward batch approach for synthesizing highly uniform, deformable and tunable hydrogel particles, which can also be easily derivatized to trigger specific cellular behavior. The 3D shape of such particles can be resolved with superresolution (<50 nm) accuracy using conventional confocal microscopy. We introduce a computational method that allows inference of surface traction forces with high sensitivity (~10 Pa) directly from the particle shape. We illustrate the potential and flexibility of this approach by revealing surprising subcellular force patterns throughout phagocytic engulfment and measuring dynamics of cytotoxic T cell force exertion in the immunological synapse. This strategy can readily be adapted for studying cellular forces in a wide range of applications. <50 nm precision. Finally, we solve the inverse problem of inferring the displacement field and traction forces from the measured particle shape and traction-free regions. This is accomplished by iteratively minimizing a cost function consisting of contributions from shape mismatch, residual tractions, and the elastic energy, and is enabled by a fast spherical harmonics-based method 17 . We illustrate the potential of this MP-TFM method by revealing subcellular details of the mechanical interaction of macrophages with their targets during phagocytosis, as well as the dynamics of force exertion in the T cell immunological synapse.

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3D Microenvironment Stiffness Regulates Tumor Spheroid Growth and Mechanics via p21 and ROCK

et al. 2019

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The mechanical properties of cancer cells and their microenvironment contribute to breast cancer progression. While mechanosensing has been extensively studied using 2D substrates, much less is known about it in a physiologically more relevant 3D context. Here it is demonstrated that breast cancer tumor spheroids, growing in 3D polyethylene glycol‐heparin hydrogels, are sensitive to their environment stiffness. During tumor spheroid growth, compressive stresses of up to 2 kPa build up, as quantitated using elastic polymer beads as stress sensors. Atomic force microscopy reveals that tumor spheroid stiffness increases with hydrogel stiffness. Also, constituent cell stiffness increases in a Rho associated kinase (ROCK)‐ and F‐actin‐dependent manner. Increased hydrogel stiffness correlated with attenuated tumor spheroid growth, a higher proportion of cells in G0/G1 phase, and elevated levels of the cyclin‐dependent kinase inhibitor p21. Drug‐mediated ROCK inhibition not only reverses cell stiffening upon culture in stiff hydrogels but also increases tumor spheroid growth. Taken together, a mechanism by which the growth of a tumor spheroid can be regulated via cytoskeleton rearrangements in response to its mechanoenvironment is revealed here. Thus, the findings contribute to a better understanding of how cancer cells react to compressive stress when growing under confinement in stiff environments.

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Standardized microgel beads as elastic cell mechanical probes

Abstract: Standardized polyacrylamide microgel beads as novel tools to calibrate experiments in biomechanics and to measure stresses in complex tissues.

Cited by 91 publications

References 93 publications

Dancing with the Cells: Acoustic Microflows Generated by Oscillating Cells

Dancing with the Cells: Acoustic Microflows Generated by Oscillating Cells

Superresolved microparticle traction force microscopy reveals subcellular force patterns in immune cell-target interactions

3D Microenvironment Stiffness Regulates Tumor Spheroid Growth and Mechanics via p21 and ROCK

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