Cell Shape and Substrate Rigidity Both Regulate Cell Stiffness

Tee, Shang You; Fu, Jianping; Chen, Christopher; Janmey, Paul A.

doi:10.1016/j.bpj.2010.12.3744

Cited by 375 publications

(350 citation statements)

References 13 publications

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“…It should be noted that the experiments behind this criterion investigated samples which were significantly softer than their underlying substrate and that it cannot be said with certainty that the results reported were not influenced by the relatively low stiffness of the underlying substrate. However, the reported values of cellular stiffness are within the range of previously reported data [17,54 -56], while previous work has confirmed that cells alter their stiffness as a result of changes in the stiffness of their underlying substrate [57,58]. Cell morphology is a widely used indicator of the differentiation stage of osteogenic cells [59,60], and MC3T3-E1 cells have previously been shown to alter their morphology in response to the same changes in the extracellular mechanical environment as induced here [11].…”

Section: Discussionsupporting

confidence: 85%

Cell morphology and focal adhesion location alters internal cell stress

Mullen

Vaughan

Voisin

et al. 2014

J. R. Soc. Interface.

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Extracellular mechanical cues have been shown to have a profound effect on osteogenic cell behaviour. However, it is not known precisely how these cues alter intracellular mechanics to initiate changes in cell behaviour. In this study, a combination of in vitro culture of MC3T3-E1 cells and finiteelement modelling was used to investigate the effects of passive differences in substrate stiffness on intracellular mechanics. Cells on collagen-based substrates were classified based on the presence of cell processes and the dimensions of various cellular features were quantified. Focal adhesion (FA) density was quantified from immunohistochemical staining, while cell and substrate stiffnesses were measured using a live-cell atomic force microscope. Computational models of cell morphologies were developed using an applied contraction of the cell body to simulate active cell contraction. The results showed that FA density is directly related to cell morphology, while the effect of substrate stiffness on internal cell tension was modulated by both cell morphology and FA density, as investigated by varying the number of adhesion sites present in each morphological model. We propose that the cells desire to achieve a homeostatic stress state may play a role in osteogenic cell differentiation in response to extracellular mechanical cues.

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Section: Discussionsupporting

confidence: 85%

Cell morphology and focal adhesion location alters internal cell stress

Mullen

Vaughan

Voisin

et al. 2014

J. R. Soc. Interface.

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“…3C, our findings demonstrated that the elastic modulus of patterned endothelial cells increased with increasing matrix rigidity, in agreement with previous reports on fibroblasts. 24,25 By combining these results, we show that the cell relaxation time decreased with the cell elastic modulus (Fig. 3D), confirming that the cell relaxation dynamics reflects the internal tension of endothelial cells and can be used as a reliable parameter to characterize the pre-stress in adherent cells.…”

Section: Cellular Relaxation Dynamics Is Modulated By Matrix Stiffnesssupporting

confidence: 65%

Probing cytoskeletal pre-stress and nuclear mechanics in endothelial cells with spatiotemporally controlled (de-)adhesion kinetics on micropatterned substrates

Versaevel

Riaz

Corne

et al. 2016

Cell Adhesion & Migration

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The mechanical properties of living cells reflect their propensity to migrate and respond to external forces. Both cellular and nuclear stiffnesses are strongly influenced by the rigidity of the extracellular matrix (ECM) through reorganization of the cyto-and nucleoskeletal protein connections. Changes in this architectural continuum affect cell mechanics and underlie many pathological conditions. In this context, an accurate and combined quantification of the mechanical properties of both cells and nuclei can contribute to a better understanding of cellular (dys-) function. To address this challenge, we have established a robust method for probing cellular and nuclear deformation during spreading and detachment from micropatterned substrates. We show that (de-)adhesion kinetics of endothelial cells are modulated by substrate stiffness and rely on the actomyosin network. We combined this approach with measurements of cell stiffness by magnetic tweezers to show that relaxation dynamics can be considered as a reliable parameter of cellular prestress in adherent cells. During the adhesion stage, large cellular and nuclear deformations occur over a long time span (>60 min). Conversely, nuclear deformation and condensed chromatin are relaxed in a few seconds after detachment. Finally, our results show that accumulation of farnesylated prelamin leads to modifications of the nuclear viscoelastic properties, as reflected by increased nuclear relaxation times. Our method offers an original and non-intrusive way of simultaneously gauging cellular and nuclear mechanics, which can be extended to high-throughput screens of pathological conditions and potential countermeasures.

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“…2,3,[6][7][8][9][10][11][12][13] The Atomic Force Microscope 14,15 (AFM) has proved to be a valuable tool for the quantitative characterization of static and frequency-dependent mechanical properties of micro-and nanostructures, including biological specimens, [16][17][18][19][20][21][22] thanks to its ability to sense and apply nanoscale forces, and to capture the three-dimensional topography of samples in different environments, including physiological buffers. Several papers report on the measurement by AFM of modulations in cellular elasticity induced by variations in the environmental conditions, like drugs targeting specific cytoskeletal components, [23][24][25] by changes in the elasticity and surface energy of the substrate, [26][27][28] as well as by the correlation between cells' elasticity and their patho-physiological state, including cancer diseases. [29][30][31][32][33][34] In light of these considerations, it is not unreasonable to think about future applications of AFM in bio-nano-medicine, with particular regard to the pre-diagnosis a) alessandro.podesta@mi.infn.it of cancer diseases, drug testing, or regenerative medicine.…”

Section: Introductionmentioning

confidence: 99%

Nanomechanical and topographical imaging of living cells by atomic force microscopy with colloidal probes

Puricelli

Galluzzi

Schulte

et al. 2015

Review of Scientific Instruments

159

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Atomic Force Microscopy (AFM) has a great potential as a tool to characterize mechanical and morphological properties of living cells; these properties have been shown to correlate with cells' fate and patho-physiological state in view of the development of novel early-diagnostic strategies. Although several reports have described experimental and technical approaches for the characterization of cellular elasticity by means of AFM, a robust and commonly accepted methodology is still lacking.Here we show that micrometric spherical probes (also known as colloidal probes) are well suited for performing a combined topographic and mechanical analysis of living cells, with spatial resolution suitable for a complete and accurate mapping of cell morphological and elastic properties, and superior reliability and accuracy in the mechanical measurements with respect to conventional and widely used sharp AFM tips. We address a number of issues concerning the nanomechanical analysis, including the applicability of contact mechanical models and the impact of a constrained contact geometry on the measured Young's modulus (the finite-thickness effect). We have tested our protocol by imaging living PC12 and MDA-MB-231 cells, in order to demonstrate the importance of the correction of the finite-thickness effect and the change in Young's modulus induced by the action of a cytoskeleton-targeting drug.

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Cell Shape and Substrate Rigidity Both Regulate Cell Stiffness

Cited by 375 publications

References 13 publications

Cell morphology and focal adhesion location alters internal cell stress

Cell morphology and focal adhesion location alters internal cell stress

Probing cytoskeletal pre-stress and nuclear mechanics in endothelial cells with spatiotemporally controlled (de-)adhesion kinetics on micropatterned substrates

Nanomechanical and topographical imaging of living cells by atomic force microscopy with colloidal probes

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