Stiffness Sensing and Cell Motility: Durotaxis and Contact Guidance

Feng, Junbo; Levine, Herbert; Mao, Xiaoming; Sander, Leonard M.

doi:10.1101/320705

Cited by 11 publications

(14 citation statements)

References 30 publications

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“…Furthermore, the straight configuration of FCs that is augmented due to nonlinear elasticity can form a structural guide to direct cell migration. Many types of migrating cells exhibit directionally persistent migration along the direction of aligned elements [75,76].…”

Section: Discussionmentioning

confidence: 99%

Force chains in cell–cell mechanical communication

Mann

Sopher

Goren

et al. 2019

J. R. Soc. Interface.

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Force chains (FCs) are a key determinant of the micromechanical properties and behaviour of heterogeneous materials, such as granular systems. However, less is known about FCs in fibrous materials, such as the networks composing the extracellular matrix (ECM) of biological systems. Using a finite-element computational model, we simulated the contraction of a single cell and two nearby cells embedded in two-dimensional fibrous elastic networks and analysed the tensile FCs that developed in the ECM. The role of ECM nonlinear elasticity on FC formation was evaluated by considering linear and nonlinear, i.e. exhibiting ‘buckling’ and/or ‘strain-stiffening’, stress–strain curves. The effect of the degree of cell contraction and network coordination value was assessed. We found that nonlinear elasticity of the ECM fibres influenced the structure of the FCs, facilitating the transition towards more distinct chains that were less branched and more radially oriented than the chains formed in linear elastic networks. When two neighbouring cells contract, a larger number of FCs bridged between the cells in nonlinear networks, and these chains had a larger effective rigidity than the chains that did not reach a neighbouring cell. These results suggest that FCs function as a route for mechanical communication between distant cells and highlight the contribution of ECM fibre nonlinear elasticity to the formation of FCs.

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Section: Discussionmentioning

confidence: 99%

Force chains in cell–cell mechanical communication

Mann

Sopher

Goren

et al. 2019

J. R. Soc. Interface.

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“…In addition, the transport properties (e.g., macromolecule diffusivity) [32,[37][38][39][40][41][42][43][44][45][46] and mechanical properties (e.g., elastic moduli, bulk rheology, stress distribution, etc.) [14,16,18,35,[47][48][49][50][51][52][53] of biopolymer network, which are respectively crucial to the chemical and mechanical signalling between the cells, strongly depend on the network microstructure.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous force network in 3D cellularized collagen networks

Liang¹,

Jones²,

Chen³

et al. 2016

Phys. Biol.

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*Biopolymer Networks play an important role in coordinating and regulating collective cellular dynamics via a number of signaling pathways. Here, we investigate the mechanical response of a model biopolymer network due to the active contraction of embedded cells. Specifically, a graph (bond-node) model derived from confocal microscopy data is used to represent the network microstructure, and cell contraction is modeled by applying correlated displacements at specific nodes, representing the focal adhesion sites. A force-based stochastic relaxation method is employed to obtain force-balanced network under cell contraction. We find that the majority of the forces are carried by a small number of heterogeneous force chains emitted from the contracting cells. The force chains consist of fiber segments that either possess a high degree of alignment before cell contraction or are aligned due to the reorientation induced by cell contraction. Large fluctuations of the forces along different force chains are observed. Importantly, the decay of the forces along the force chains is significantly slower than the decay of radially averaged forces in the system. These results suggest that the fibreous nature of biopolymer network structure can support long-range force transmission and thus, long-range mechanical signaling between cells.

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“…Feng et al. ( Feng et al., 2018 ) showed that if FA degradation is higher in the back than in the front and FAs mature under applied force, then a cell can durotact. Based on experimental observations, Novikova et al.…”

Section: Discussionmentioning

confidence: 99%

“…As a first step toward more complex matrices, we have studied how cell spreading, elongation, and durotaxis are affected by inhomogeneity in substrate stiffness (uniform noise, Figures S4 A–C) and explored the effect of small-scale spatial inhomogeneities on cell elongation ( Figures S4 D–L). In our ongoing work, we are extending the model to better represent the fibrous and strain-stiffening properties of natural ECMs ( Hall et al, 2016 ; Han et al, 2018 ; van Helvert and Friedl, 2016 ) by incorporating discrete ECM models ( Feng et al., 2015 , 2018 ; Kim et al., 2017 ; Licup et al, 2015 ) with our cell-based models. Although the effect of traction forces propagates further into nonlinearly elastic, fibrous ECMs ( Ma et al., 2013 ), the key results of our model are based on increased stability of FAs on strained matrices and so, will likely still apply.…”

Section: Discussionmentioning

confidence: 99%

Cell Shape and Durotaxis Explained from Cell-Extracellular Matrix Forces and Focal Adhesion Dynamics

Rens

Merks

2020

iScience

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Summary Many cells are small and rounded on soft extracellular matrices (ECM), elongated on stiffer ECMs, and flattened on hard ECMs. Cells also migrate up stiffness gradients (durotaxis). Using a hybrid cellular Potts and finite-element model extended with ODE-based models of focal adhesion (FA) turnover, we show that the full range of cell shape and durotaxis can be explained in unison from dynamics of FAs, in contrast to previous mathematical models. In our 2D cell-shape model, FAs grow due to cell traction forces. Forces develop faster on stiff ECMs, causing FAs to stabilize and, consequently, cells to spread on stiff ECMs. If ECM stress further stabilizes FAs, cells elongate on substrates of intermediate stiffness. We show that durotaxis follows from the same set of assumptions. Our model contributes to the understanding of the basic responses of cells to ECM stiffness, paving the way for future modeling of more complex cell-ECM interactions.

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Stiffness Sensing and Cell Motility: Durotaxis and Contact Guidance

Cited by 11 publications

References 30 publications

Force chains in cell–cell mechanical communication

Force chains in cell–cell mechanical communication

Heterogeneous force network in 3D cellularized collagen networks

Cell Shape and Durotaxis Explained from Cell-Extracellular Matrix Forces and Focal Adhesion Dynamics

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