Force transmission in migrating cells Fournier, Maxime F; Sauser, Roger; Ambrosi, Davide ...
The Journal of cell biology,
01/2010, Volume:
188, Issue:
2
Journal Article
Peer reviewed
Open access
During cell migration, forces generated by the actin cytoskeleton are transmitted through adhesion complexes to the substrate. To investigate the mechanism of force generation and transmission, we ...analyzed the relationship between actin network velocity and traction forces at the substrate in a model system of persistently migrating fish epidermal keratocytes. Front and lateral sides of the cell exhibited much stronger coupling between actin motion and traction forces than the trailing cell body. Further analysis of the traction-velocity relationship suggested that the force transmission mechanisms were different in different cell regions: at the front, traction was generated by a gripping of the actin network to the substrate, whereas at the sides and back, it was produced by the network's slipping over the substrate. Treatment with inhibitors of the actin-myosin system demonstrated that the cell body translocation could be powered by either of the two different processes, actomyosin contraction or actin assembly, with the former associated with significantly larger traction forces than the latter.
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This work investigates the mechano-biological features of cells cultured in monolayers in response to different osmotic conditions. In-vitro experiments have been performed to quantify the long-term ...effects of prolonged osmotic stresses on the morphology and proliferation capacity of glioblastoma cells. The experimental results highlight that both hypotonic and hypertonic conditions affect the proliferative rate of glioblastoma cells on different cell cycle phases. Moreover, glioblastoma cells in hypertonic conditions display a flattened and elongated shape. The latter effect is explained using a nonlinear elastic model for the single cell. Due to a crossover between the free energy contributions related to the cytosol and the cytoskeletal fibers, a critical osmotic stress determines a morphological transition from a uniformly compressed to an elongated shape.
Tumour cells usually live in an environment formed by other host cells, extra-cellular matrix and extra-cellular liquid. Cells duplicate, reorganise and deform while binding each other due to ...adhesion molecules exerting forces of measurable strength. In this paper, a macroscopic mechanical model of solid tumour is investigated which takes such adhesion mechanisms into account. The extracellular matrix is treated as an elastic compressible material, while, in order to define the relationship between stress and strain for the cellular constituents, the deformation gradient is decomposed in a multiplicative way distinguishing the contribution due to growth, to cell rearrangement and to elastic deformation. On the basis of experimental results at a cellular level, it is proposed that at a macroscopic level there exists a yield condition separating the elastic and dissipative regimes. Previously proposed models are obtained as limit cases, e.g. fluid-like models are obtained in the limit of fast cell reorganisation and negligible yield stress. A numerical test case shows that the model is able to account for several complex interactions: how tumour growth can be influenced by stress, how and where it can generate cell reorganisation to release the stress level, how it can lead to capsule formation and compression of the surrounding tissue.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
One of the most remarkable differences between classical engineering materials and living matter is the ability of the latter to grow and remodel in response to diverse stimuli. The mechanical ...behaviour of living matter is governed not only by an elastic or viscoelastic response to loading on short time scales up to several minutes, but also by often crucial growth and remodelling responses on time scales from hours to months. Phenomena of growth and remodelling play important roles, for example during morphogenesis in early life as well as in homeostasis and pathogenesis in adult tissues, which often adapt to changes in their chemo-mechanical environment as a result of ageing, diseases, injury or surgical intervention. Mechano-regulated growth and remodelling are observed in various soft tissues, ranging from tendons and arteries to the eye and brain, but also in bone, lower organisms and plants. Understanding and predicting growth and remodelling of living systems is one of the most important challenges in biomechanics and mechanobiology. This article reviews the current state of growth and remodelling as it applies primarily to soft tissues, and provides a perspective on critical challenges and future directions.
This paper investigates the role of mechanics in the morphogenesis of the annulus of the mitral valve. We represent the annulus in its embryonic stage as an elastic ring and we perform a mechanical ...simulation of the development process applying a distributed torque on the rod: because of the mechanical action of the other growing cardiac chambers on the atrio-ventricular region, it departs from a planar circular shape. The numerical integration of the mathematical rod model subject to a bending load yields a shape very near to the one reported in the medical literature as anatomical reference for healthy patients. To make the comparison quantitative, we illustrate a numerical approach to match two curves in 3D defining their distance in a proper mathematical way. Such a methodology is first applied to compare the annular shape resulting from the mechanical model with an anatomical reference “master” shape and it is then applied to set to clinical data extracted from MRI for a cohort of healthy patients. The good agreement among anatomical master description, numerical mechanical model, and clinical data supports our speculation about a possible role of mechanics in determining the shape of the mitral valve.
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This book offers a mathematical update of the state of the art of the research in the field of mathematical and numerical models of the circulatory system. It is structured into different chapters, ...written by outstanding experts in the field. Many fundamental issues are considered, such as: the mathematical representation of vascular geometries extracted from medical images, modelling blood rheology and the complex multilayer structure of the vascular tissue, and its possible pathologies, the mechanical and chemical interaction between blood and vascular walls, and the different scales coupling local and systemic dynamics. All of these topics introduce challenging mathematical and numerical problems, demanding for advanced analysis and efficient simulation techniques, and pay constant attention to applications of relevant clinical interest. This book is addressed to graduate students and researchers in the field of bioengineering, applied mathematics and medicine, wishing to engage themselves in the fascinating task of modeling the cardiovascular system or, more broadly, physiological flows.
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FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Concentrated cell suspensions exhibit different mechanical behavior depending on the mechanical stress or deformation they undergo. They have a mixed rheological nature: cells behave elastically or ...viscoelastically, they can adhere to each other whereas the carrying fluid is usually Newtonian. We report here on a new elasto-visco-plastic model which is able to describe the mechanical properties of a concentrated cell suspension or aggregate. It is based on the idea that the rearrangement of adhesion bonds during the deformation of the aggregate is related to the existence of a yield stress in the macroscopic constitutive equation. We compare the predictions of this new model with five experimental tests: steady shear rate, oscillatory shearing tests, stress relaxation, elastic recovery after steady prescribed deformation, and uniaxial compression tests. All of the predictions of the model are shown to agree with these experiments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In vertebrates, networks of capillary vessels supply tissues with nutrients. Capillary patterns are closely mimicked by endothelial cells cultured on basement membrane proteins that allow single ...randomly dispersed cells to self‐organize into vascular networks. Here we provide a model including chemoattraction as the fundamental mechanism for cell‐to‐cell communication in order to identify key parameters in the complexity of the formation of vascular patterns. By flanking biological experiments, theoretical insights and numerical simulations, we provide strong evidence that endothelial cell number and the range of activity of a chemoattractant factor regulate vascular network formation and size. We propose a mechanism linking the scale of formed endothelial structures to the range of cell‐to‐cell interaction mediated by the release of chemoattractants.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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