Necking and failure of constrained 3D microtissues induced by cellular tension

Wang, Hailong; Svoronos, Alexander A.; Boudou, Thomas; Sakar, Mahmut Selman; Schell, Jacquelyn Y.; Morgan, Jeffrey R.; Chen, Christopher; Shenoy, Vivek B.

doi:10.1073/pnas.1313662110

Cited by 50 publications

(65 citation statements)

References 39 publications

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“…If the contractility is very large, the gel may rupture at short times: one then has to describe self-rupturing systems 36,37 . If the active elements are very dense, one can have active jammed states 38,39 .…”

Section: Active Gels In Other Domains Of Physicsmentioning

confidence: 99%

Active gel physics

2015

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The mechanical behaviour of cells is largely controlled by a structure that is fundamentally out of thermodynamic equilibrium: a network of crosslinked filaments subjected to the action of energy-transducing molecular motors. The study of this kind of active system was absent from conventional physics and there was a need for both new theories and new experiments. The field that has emerged in recent years to fill this gap is underpinned by a theory that takes into account the transduction of chemical energy on the molecular scale. This formalism has advanced our understanding of living systems, but it has also had an impact on research in physics per se. Here, we describe this developing field, its relevance to biology, the novelty it conveys to other areas of physics and some of the challenges in store for the future of active gel physics.

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Section: Active Gels In Other Domains Of Physicsmentioning

confidence: 99%

Active gel physics

2015

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“…The quiescent contractility has been estimated in our previous work to be r 0 ¼ 0.5 kPa [31]. The size of a myoblast is taken to be r ¼ 10 mm [32].…”

Section: Determination Of the Chemo-mechanical Coupling Parameters Frmentioning

confidence: 99%

A chemo-mechanical free-energy-based approach to model durotaxis and extracellular stiffness-dependent contraction and polarization of cells

Shenoy¹,

Wang²,

Xiao³

2016

Interface Focus.

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We propose a chemo-mechanical model based on stress-dependent recruitment of myosin motors to describe how the contractility, polarization and strain in cells vary with the stiffness of their surroundings and their shape. A contractility tensor, which depends on the distribution of myosin motors, is introduced to describe the chemical free energy of the cell due to myosin recruitment. We explicitly include the contributions to the free energy that arise from mechanosensitive signalling pathways (such as the SFX, Rho-Rock and MLCK pathways) through chemo-mechanical coupling parameters. Taking the variations of the total free energy, which consists of the chemical and mechanical components, in accordance with the second law of thermodynamics provides equations for the temporal evolution of the active stress and the contractility tensor. Following this approach, we are able to recover the well-known Hill relation for active stresses, based on the fundamental principles of irreversible thermodynamics rather than phenomenology. We have numerically implemented our free energy-based approach to model spatial distribution of strain and contractility in (i) cells supported by flexible microposts, (ii) cells on two-dimensional substrates, and (iii) cells in three-dimensional matrices. We demonstrate how the polarization of the cells and the orientation of stress fibres can be deduced from the eigenvalues and eigenvectors of the contractility tensor. Our calculations suggest that the chemical free energy of the cell decreases with the stiffness of the extracellular environment as the cytoskeleton polarizes in response to stress-dependent recruitment of molecular motors. The mechanical energy, which includes the strain energy and motor potential energy, however, increases with stiffness, but the overall energy is lower for cells in stiffer environments. This provides a thermodynamic basis for durotaxis, whereby cells preferentially migrate towards stiffer regions of the extracellular environment. Our models also explain, from an energetic perspective, why the shape of the cells can change in response to stiffness of the surroundings. The effect of the stiffness of the nucleus on its shape and the orientation of the stress fibres is also studied for all the above geometries. Along with making testable predictions, we have estimated the magnitudes of the chemo-mechanical coupling parameters for myofibroblasts based on data reported in the literature.

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“…The total deformation gradient is expressed as F ¼ vx=vX. The deformation gradient of the blood clot or the total strain ðFÞ is multiplicatively decomposed into the stress of the platelet-RBC-fibrin element and the RBC-fibrin element that is in series (27):…”

Section: Relation Of the Model To Contracting Clotsmentioning

confidence: 99%

“…Mathematical models have been used to assess the feedback effect that matrix stiffness has on the mechanics of active contractile cells (26) and to describe morphological changes and mechanical responses in an active elastic material (27). Given the structural similarities between previously described contracting microtissue and contracting blood clots, we chose to couple the basis of these aforementioned mathematical models with what is known about the individual components of clots to, for the first time to our knowledge, couple active contractile mechanics with a viscoelastic matrix (Fig.…”

Section: Introductionmentioning

confidence: 99%

Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction

Tutwiler

Wang

Litvinov

et al. 2017

Biophysical Journal

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Blood clot contraction (retraction) is driven by platelet-generated forces propagated by the fibrin network and results in clot shrinkage and deformation of erythrocytes. To elucidate the mechanical nature of this process, we developed a model that combines an active contractile motor element with passive viscoelastic elements. Despite its importance for thrombosis and wound healing, clot contraction is poorly understood. This model predicts how clot contraction occurs due to active contractile platelets interacting with a viscoelastic material, rather than to the poroelastic nature of fibrin, and explains the observed dynamics of clot size, ultrastructure, and measured forces. Mechanically passive erythrocytes and fibrin are present in series and parallel to active contractile cells. This mechanical interplay induces compressive and tensile resistance, resulting in increased contractile force and a reduced extent of contraction in the presence of erythrocytes. This experimentally validated model provides the fundamental mechanical basis for understanding contraction of blood clots.

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Necking and failure of constrained 3D microtissues induced by cellular tension

Cited by 50 publications

References 39 publications

Active gel physics

Active gel physics

A chemo-mechanical free-energy-based approach to model durotaxis and extracellular stiffness-dependent contraction and polarization of cells

Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction

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