Biology subjects

Ben Amar, M.

Publications and source records attributed to Ben Amar, M..

7 recordsLinked to original sources

bioRxiv2024

Physical forces drive C. elegans embryonic deformation

The abnormal development of embryos is closely linked to abnormal cell division and elongation, but the underlying mechanism remains to be elucidated. The embryonic development of C elegans embryo is different because it occurs without cell proliferation or cell rearrangement. Here, we focus on a spectacular 4-fold elongation that is achieved approximately 3 hours before the egg shell hatches and results from active filament networks. The body shape is represented by an inhomogeneous cylinder, which allows us to assess the active stresses induced by the actomyosin network located in the cortex and the muscles in ventral position near the epidermis. By considering the specific embryo configuration, we can quantitatively obtain the contractile forces induced by actomyosin filaments and muscles for a bending torsion event with defined curvature. We find that the active stress induced by actomyosin molecular motors or muscles increases with elongation and bending curvature, while also varying with radius. Both elongation and torsional deformation contribute to increased moment magnitudes that explain the dynamics of the embryo in the egg. Our results highlight the complex interplay between biomechanical factors in modulating embryonic deformation.

biophysics↗

bioRxiv2024

How cancer-associated fibroblasts promote T cell exclusion in human lung tumors: a physical perspective

The tumor stroma is a tissue composed primarily of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions, such as nutrient support and waste removal, are altered during malignancy. Tumor cells transform fibroblasts into cancer-associated fibroblasts, which have important immunosuppressive activity on which growth, invasion, and metastasis depend. These activated fibroblasts prevent immune cell infiltration into the tumor nest, thereby promoting cancer progression and inhibiting T-cell-based immunotherapy. To understand these complex interactions, we measure the density of different cell types in the stroma using immunohistochemistry techniques on tumor samples from lung cancer patients. We incorporate these data, and also known information on cell proliferation rates and relevant biochemical interactions, into a minimal dynamical system with few parameters. A spatio-temporal approach to the inhomogeneous environment explains the cell distribution and fate of lung carcinomas. The model reproduces that cancer-associated fibroblasts act as a barrier to tumor growth, but also reduce the efficiency of the immune response. The final outcome depends on the parameter values for each patient and leads to either tumor invasion, persistence, or eradication as a result of the interplay between cancer cell growth, T-cell cytotoxic activity, and fibroblast attraction, activation, and spatial dynamics. Our conclusion is that a wide spectrum of scenarios exists as a result of the competition between the characteristic times of cancer cell growth and the activity rates of the other species. Nevertheless, distinct trajectories and patterns allow quantitative predictions that may help in the selection of new therapies and personalized protocols. We conclude with different options for further modeling. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/575824v3_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@156ac4forg.highwire.dtl.DTLVardef@14a9a19org.highwire.dtl.DTLVardef@cafebeorg.highwire.dtl.DTLVardef@11aa3bf_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

biophysics↗

bioRxiv2023

Onsager's variational principle in proliferating biological tissues, in presenceof activity and anisotropy

A hallmark of biological cells is their ability to proliferate and of tissues their ability to grow. This is common in morphogenesis and embryogenesis but also in pathological conditions such as tumour growth. To consider these tissues from a physical point of view, it is necessary to derive fundamental relationships, in particular for velocities and density components, taking into account growth terms, chemical factors and the symmetry of cells and tissues. The aim is then to develop a consistent coarse-grained approach to these complex systems, which exhibit proliferation, disorder, anisotropy and activity at small scales. To this end, Onsagers variational principle allows the systematic derivation of flux-force relations in systems out of equilibrium and the principle of the extremum of dissipation, first formulated by Rayleigh and revisited by Onsager, finally leads to a consistent formulation for a continuous approach in terms of a coupled set of partial differential equations. Considering the growth and death rates as fluxes, as well as the chemical reactions driving the cellular activities, we derive the momentum equations based on a leading order physical expansion. Furthermore, we illustrate the different interactions for systems with nematic or polar order at small scales, and numerically solve the resulting system of partial differential equations in relevant biophysical growth examples. To conclude, we show that Onsagers variational principle is useful for systematically exploring the different scenarios in proliferating systems, and how morphogenesis depends on these interactions.

biophysics↗

bioRxiv2023

Cyclic muscle contractions reinforce the acto-myosin motors and mediate the full elongation of C. elegans embryo

The paramount importance of mechanical forces in morphogenesis and embryogenesis is widely recognized, but understanding the mechanism at the cellular and molecular level remains challenging. Because of its simple internal organization, Caenorhabditis elegans is a rewarding system of study. As demonstrated experimentally, after an initial period of steady elongation driven by the actomyosin network, muscle contractions operate a quasi-periodic sequence of bending, rotation and torsion, that leads to the final 4-fold size of the embryo before hatching. How actomyosin and muscles contribute to embryonic elongation is investigated here theoretically. A filamentary elastic model that converts stimuli generated by biochemical signals in the tissue into driving forces, explains embryonic deformation under actin bundles and muscle activity, and dictates mechanisms of late elongation based on the effects of energy conversion and dissipation. We quantify this dynamic transformation by stretches applied to a cylindrical structure that mimics the body shape in finite elasticity, obtaining good agreement and understanding for both wild-type and mutant embryos at all stages.

biophysics↗

bioRxiv2022

Minimizing the elastic energy of growing leaves by conformal mapping

During morphogenesis, the shape of living species results from growth, stress relaxation and remodeling. When the growth does not generate any stress, the body shape only reflects the growth density. In two dimensions, we show that stress free configurations are simply determined by the time evolution of a conformal mapping which concerns not only the boundary but also the displacement field during an arbitrary period of time inside the sample. Fresh planar leaves are good examples for our study: they have no elastic stress, almost no weight, and their shape can be easily represented by holomorphic functions. The growth factor, isotropic or anisotropic, is related to the metrics between the initial and current conformal maps. By adjusting the mathematical shape function, main characteristics such as tips (convex or concave or sharp-pointed), undulating borders and veins, can be mathematically recovered, which are in good agreement with observations. It is worth mentioning that this flexible method allows to study complex morphologies of growing leaves such as the fenestration process in Monstera deliciosa, and can also shed light on many other 2D biological patterns.

biophysics↗

bioRxiv2021

Modeling the mechanics of growing epithelia with a bilayer plate theory

Epithelia, which consists of cell sheets lying on a substrate, are prevalent structures of multi-cellular organisms. The physical basis of epithelial morphogenesis has been intensely investigated in recent years. However, as 2D mechanics focused most attention, we still lack a rigorous description of how the mechanical interactions between the cell layer and its substrate can lead to 3D distortions. This work provides a complete description of epithelial mechanics using the most straightforward model of an epithelium: a thin elastic bilayer. We first provide experimental evidence in Drosophila tissues that localized alterations of the cell-substrate (the extracellular matrix) can lead to profound 3D shape changes in epithelia. We then develop an analytical model modifying the Foppl-von Karman equation with growth for bilayers. We provide a complete description of all contributions from biophysical characteristics of epithelia. We show how any localized inhomogeneity of stiffness or thickness drastically changes the bending process when the two layers grow differently. Comparison with finite-element simulations and experiments performed on Drosophila wing imaginal discs validate this approach for thin epithelia.

biophysics↗

bioRxiv2016

The interplay of stiffness and force anisotropies drive embryo elongation

The morphogenesis of tissues, like the deformation of an object, results from the interplay between their material properties and the mechanical forces exerted on them. Whereas the importance of mechanical forces in influencing cell behaviour is widely recognized, the importance of tissue material properties, in particular stiffness, has received much less attention. Using C. elegans as a model, we examine how both aspects contribute to embryonic elongation. Measuring the opening shape of the epidermal actin cortex after laser nano-ablation, we assess the spatiotemporal changes of actomyosin-dependent force and stiffness along the antero-posterior and dorso-ventral axis. Experimental data and analytical modelling show that myosin II-dependent force anisotropy within the lateral epidermis, and stiffness anisotropy within the fiber-reinforced dorso-ventral epidermis are critical to drive embryonic elongation. Together, our results establish a quantitative link between cortical tension, material properties and morphogenesis of an entire embryo.

developmental biology↗