1,720,984 research outputs found
Numerical Methods to Compute Stresses and Displacements from Cellular Forces: Application to the Contraction of Tissue
No full textWe consider a mathematical model for wound contraction, which is based on solving a momentum balance under the assumptions of isotropy, homogeneity, Hooke's Law, in-finitesimal strain theory and point forces exerted by cells. However, point forces, described by Dirac Delta distributions lead to a singular solution, which in many cases may cause trouble to finite element methods due to a low degree of regularity. Hence, we consider several alternatives to address point forces, that is, whether to treat the region covered by the cells that exert forces as part of the computational domain or as 'holes' in the computational domain. The formalisms develop into the immersed boundary approach and the 'hole approach', respectively. Consistency between these approaches is verified in a theoretical setting, but also confirmed computationally. However, the 'hole approach' is much more expensive and complicated for its need of mesh adaptation in the case of migrating cells while it increases the numerical accuracy, which makes it hard to adapt to the multi-cell model. Therefore, for multiple cells, we consider the polygon that is used to approximate the boundary of cells that exert contractile forces. It is found that a low degree of polygons, in particular triangular or square shaped cell boundaries, already give acceptable results in engineering precision, so that it is suitable for the situation with a large amount of cells in the computational domain.Authors acknowledge the China Scholarship Council (CSC) for financial support to this project
Agent-based modelling and parameter sensitivity analysis with a finite-element method for skin contraction
No full textIn this paper, we extend the model of wound healing by Boon et al. (J Biomech 49(8):1388–1401, 2016). In addition to explaining the model explicitly regarding every component, namely cells, signalling molecules and tissue bundles, we categorized fibroblasts as regular fibroblasts and myofibroblasts. We do so since it is widely documented that myofibroblasts play a significant role during wound healing and skin contraction and that they are the main phenotype of cells that is responsible for the permanent deformations. Furthermore, we carried out some sensitivity tests of the model by modifying certain parameter values, and we observe that the model shows some consistency with several biological phenomena. Using Monte Carlo simulations, we found that there is a significant strong positive correlation between the final wound area and the minimal wound area. The high correlation between the wound area after 4 days and the final/minimal wound area makes it possible for physicians to predict the most probable time evolution of the wound of the patient. However, the collagen density ratio at the time when the wound area reaches its equilibrium and minimum, cannot indicate the degree of wound contractions, whereas at the 4th day post-wounding, when the collagen is accumulating from null, there is a strong negative correlation between the area and the collagen density ratio. Further, under the circumstances that we modelled, the probability that patients will end up with 5% contraction is about 0.627.Numerical Analysi
Point forces in elasticity equation and their alternatives in multi dimensions
Full text linkDeep dermal wounds induce skin contraction as a result of the traction forcing exerted by (myo)fibroblasts on their immediate environment. These (myo)fibroblasts are skin cells that are responsible for the regeneration of collagen that is necessary for the integrity of skin We consider several mathematical issues regarding models that simulate traction forces exerted by (myo)fibroblasts. Since the size of cells (e.g. (myo)fibroblasts) is much smaller than the size of the domain of computation, one often considers point forces, modelled by Dirac Delta distributions on boundary segments of cells to simulate the traction forces exerted by the skin cells. In the current paper, we treat the forces that are directed normal to the cell boundary and toward the cell centre. Since it can be shown that there exists no smooth solution, at least not in H1 for solutions to the governing momentum balance equation, we analyse the convergence and quality of approximation. Furthermore, the expected finite element problems that we get necessitate to scrutinize alternative model formulations, such as the use of smoothed Dirac Delta distributions, or the so-called smoothed particle approach as well as the so-called ‘hole’ approach where cellular forces are modelled through the use of (natural) boundary conditions. In this paper, we investigate and attempt to quantify the conditions for consistency between the various approaches. This has resulted into error analyses in the L2-norm of the numerical solution based on Galerkin principles that entail Lagrangian basis functions. The paper also addresses well-posedness in terms of existence and uniqueness. The current analysis has been performed for the linear steady-state (hence neglecting inertia and damping) momentum equations under the assumption of Hooke's law.Numerical Analysi
Upscaling between an agent-based model (smoothed particle approach) and a continuum-based model for skin contractions
Full text linkSkin contraction is an important biophysical process that takes place during and after recovery of deep tissue injury. This process is mainly caused by fibroblasts (skin cells) and myofibroblasts (differentiated fibroblasts which exert larger pulling forces and produce larger amounts of collagen) that both exert pulling forces on the surrounding extracellular matrix (ECM). Modelling is done in multiple scales: agent-based modelling on the microscale and continuum-based modelling on the macroscale. In this manuscript we present some results from our study of the connection between these scales. For the one-dimensional case, we managed to rigorously establish the link between the two modelling approaches for both closed-form solutions and finite-element approximations. For the multi-dimensional case, we computationally evidence the connection between the agent-based and continuum-based modelling approaches.Numerical Analysi
Comparison between a phenomenological approach and a morphoelasticity approach regarding the displacement of extracellular matrix
Full text linkPlastic (permanent) deformations were earlier, modeled by a phenomenological model in Peng and Vermolen (Biomech Model Mechanobiol 19(6):2525–2551, 2020). In this manusctipt, we consider a more physics-based formulation that is based on morphoelasticity. We firstly introduce the morphoelasticity approach and investigate the impact of various input variables on the output parameters by sensitivity analysis. A comparison of both model formulations shows that both models give similar computational results. Furthermore, we carry out Monte Carlo simulations of the skin contraction model containing the morphoelasticity approach. Most statistical correlations from the two models are similar, however, the impact of the collagen density on the severeness of contraction is larger for the morphoelasticity model than for the phenomenological model.Numerical Analysi
A formalism for modelling traction forces and cell shape evolution during cell migration in various biomedical processes
No full textThe phenomenological model for cell shape deformation and cell migration Chen (BMM 17:1429–1450, 2018), Vermolen and Gefen (BMM 12:301–323, 2012), is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et al. (LC 13:340–348, 2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.</p
Physical confinement and cell proximity increase cell migration rates and invasiveness: A mathematical model of cancer cell invasion through flexible channels
Full text linkCancer cell migration between different body parts is the driving force behind cancer metastasis, which is the main cause of mortality of patients. Migration of cancer cells often proceeds by penetration through narrow cavities in locally stiff, yet flexible tissues. In our previous work, we developed a model for cell geometry evolution during invasion, which we extend here to investigate whether leader and follower (cancer) cells that only interact mechanically can benefit from sequential transmigration through narrow micro-channels and cavities. We consider two cases of cells sequentially migrating through a flexible channel: leader and follower cells being closely adjacent or distant. Using Wilcoxon’s signed-rank test on the data collected from Monte Carlo simulations, we conclude that the modelled transmigration speed for the follower cell is significantly larger than for the leader cell when cells are distant, i.e. follower cells transmigrate after the leader has completed the crossing. Furthermore, it appears that there exists an optimum with respect to the width of the channel such that cell moves fastest. On the other hand, in the case of closely adjacent cells, effectively performing collective migration, the leader cell moves 12% faster since the follower cell pushes it. This work shows that mechanical interactions between cells can increase the net transmigration speed of cancer cells, resulting in increased invasiveness. In other words, interaction between cancer cells can accelerate metastatic invasion.Analysis and Stochastic
Do Cancer Cells Collaborate During Metastasis?
No full textWe consider a model for cell deformation and cellular forces that are exerted on the immediate environment. This model is applied to the transmigration of cancer cells through narrow, deformable channels. This migration process is an important and rate-determining mechanism during the metastasis of cancer
Predicting the Efficacy of Stalk Cells Following Leading Cells Through a Micro-Channel Using Morphoelasticity and a Cell Shape Evolution Model
No full textCancer cell migration between different body parts is the driving force behind cancer metastasis, which causes mortality of patients. Migration of cancer cells often proceeds by penetration through narrow cavities in possibly stiff tissues. In our previous work [12], a model for the evolution of cell geometry is developed, and in the current study we use this model to investigate whether followers among (cancer) cells benefit from leading (cancer) cells during transmigration through microchannels and cavities. Using Wilcoxon's signed-rank text on the data collected from Monte Carlo simulations, we conclude that the transmigration time for the stalk cell is significantly smaller than for the leading cell with a p-value less than 0.0001, for the modelling set-up that we have used in this study
How can mathematics be used to improve burn care?
No full textSevere second-degree ‘partial thickness’ and third-degree ‘full thickness’ burns are characterized by damage to the dermal layer of the skin. In the dermis, specialized cells called fibroblasts play a crucial role in wound healing. These cells produce collagen, a protein that provides strength and structure to the skin. After burn injury, fibroblasts migrate to the injured area and start producing and depositing collagen to help repair the damaged tissue. While contraction is essential for closing the wound, it can also result in scar contraction (contractures), especially in more severe burns. This contraction creates stresses on the skin, which can deteriorate the mobility of joints near the burn.This article overviews the most recent research results in computer simulations of scar contraction after burns
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