Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading

Dowling, Enda P.; Ronan, William; McGarry, J. Patrick

doi:10.1016/j.actbio.2012.12.021

Cited by 35 publications

(31 citation statements)

References 84 publications

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“…This framework has previously been implemented for the modeling of stress fiber contractility in a range of cell phenotypes (30)(31)(32)(33) and for simulation of the response of cells to applied shear (34) and compression (35,36) loading. Here it is adapted for the simulation of sarcomeric filaments in cardiomyocytes on the basis that both stress fibers and sarcomeric filaments are composed of and operate via actinmyosin interactions.…”

Section: Finite-element Modeling Predicts Stress-mediated Assembly Andmentioning

confidence: 99%

Design and formulation of functional pluripotent stem cell-derived cardiac microtissues

Thavandiran

Dubois

Mikryukov

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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249

236

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Significance Robust and predictive in vitro models of human cardiac tissue function could have transformative impact on our ability to test new drugs and understand cardiac disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. In this paper, we systematically explore the design criteria for pluripotent stem cell-derived engineered cardiac tissue. Parameters such as biomechanical stress during tissue remodeling, input-cell composition, electrical stimulation, and tissue geometry are evaluated. Our results suggest that a specified combination of a 3D matrix-based microenvironment, uniaxial mechanical stress, and mixtures of cardiomyocytes and fibroblasts improves the performance and maturation state of in vitro engineered cardiac tissue.

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Section: Finite-element Modeling Predicts Stress-mediated Assembly Andmentioning

confidence: 99%

Design and formulation of functional pluripotent stem cell-derived cardiac microtissues

Thavandiran

Dubois

Mikryukov

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

249

236

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“…Stress fibre remodelling due to dynamic loading is not just important for an endothelial cell, but also for chondrocytes embedded in cartilage tissue, as investigated in the computational study of Dowling et al (2013). However, the modelling of the cell-substrate interface using a passive cohesive zone framework still represents a significant simplification.…”

Section: Case Study I: Resultsmentioning

confidence: 99%

Potential-based and non-potential-based cohesive zone formulations under mixed-mode separation and over-closure. Part I: Theoretical analysis

McGarry

Máirtín

Parry

et al. 2014

Journal of the Mechanics and Physics of Solids

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a b s t r a c tThis paper, the second of two parts, presents three novel finite element case studies to demonstrate the importance of normal-tangential coupling in cohesive zone models (CZMs) for the prediction of mixed-mode interface debonding. Specifically, four new CZMs proposed in Part I of this study are implemented, namely the potential-based MP model and the non-potential-based NP1, NP2 and SMC models. For comparison, simulations are also performed for the well established potential-based Xu-Needleman (XN) model and the non-potential-based model of van den Bosch, Schreurs and Geers (BSG model). Case study 1: Debonding and rebonding of a biological cell from a cyclically deforming silicone substrate is simulated when the mode II work of separation is higher than the mode I work of separation at the cell-substrate interface. An active formulation for the contractility and remodelling of the cell cytoskeleton is implemented. It is demonstrated that when the XN potential function is used at the cell-substrate interface repulsive normal tractions are computed, preventing rebonding of significant regions of the cell to the substrate. In contrast, the proposed MP potential function at the cell-substrate interface results in negligible repulsive normal tractions, allowing for the prediction of experimentally observed patterns of cell cytoskeletal remodelling. Case study 2: Buckling of a coating from the compressive surface of a stent is simulated. It is demonstrated that during expansion of the stent the coating is initially compressed into the stent surface, while simultaneously undergoing tangential (shear) tractions at the coating-stent interface. It is demonstrated that when either the proposed NP1 or NP2 model is implemented at the stent-coating interface mixed-mode over-closure is correctly penalised. Further expansion of the stent results in the prediction of significant buckling of the coating from the stent surface, as observed experimentally. In contrast, the BSG model does not correctly penalise mixed-mode over-closure at the stent-coating interface, significantly altering the stress state in the coating and preventing the prediction of buckling. Case study 3: Application of a displacement to the base of a bi-layered composite arch results in a symmetric sinusoidal distribution of normal and tangential traction at the arch interface. The traction defined mode mixity at the interface ranges from pure mode II at the base of the arch to pure mode I at the top of the arch. It is demonstrated that predicted debonding patterns are highly sensitive to normal-tangential coupling terms in a CZM. The NP2, XN, and BSG models exhibit a strong bias towards mode I separation at the top of the arch, while the NP1 model exhibits a bias towards mode II debonding at the base of the arch. Only the SMC model provides mode-independent behaviour in the early stages of debonding. This case study provides a practical example of the importance of the behaviour of CZMs under conditions of traction controlled mode mixity, foll...

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“…At the lower spatial scale, cell deformation metrics can be used to drive cellular-subcellular scale models, i.e. incorporating the cytoskeleton (actin and tubulin) [30], to understand the mechanical load transmission to intracellular components, in particular to the nucleus. Similar submodelling can be performed for the extracellular matrix, for example, to evaluate microstructural-level loading of collagen fibres, which may provide the relationship between macroscopic tissue damage accumulation and microscale fibre failure [31].…”

Section: High-throughput Frameworkmentioning

confidence: 99%

Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

et al. 2015

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Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading

Cited by 35 publications

References 84 publications

Design and formulation of functional pluripotent stem cell-derived cardiac microtissues

Design and formulation of functional pluripotent stem cell-derived cardiac microtissues

Potential-based and non-potential-based cohesive zone formulations under mixed-mode separation and over-closure. Part I: Theoretical analysis

Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

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