Force propagation between epithelial cells depends on active coupling and mechano-structural polarization.

Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing, and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing.

Light-driven biological actuators to probe the rheology of 3D microtissues.

The mechanical properties of biological tissues are key to their physical integrity and function. Although external loading or biochemical treatments allow the estimation of these properties globally, it remains difficult to assess how such external stimuli compare with cell-generated contractions. Here we engineer microtissues composed of optogenetically-modified fibroblasts encapsulated within collagen.

Cell size and actin architecture determine force generation in optogenetically activated cells.

Adherent cells use actomyosin contractility to generate mechanical force and to sense the physical properties of their environment, with dramatic consequences for migration, division, differentiation, and fate. However, the organization of the actomyosin system within cells is highly variable, with its assembly and function being controlled by small GTPases from the Rho family. To understand better how activation of these regulators translates into cell-scale force generation in the context of different physical environments, here we combine recent advances in non-neuronal optogenetics with micropatterning and traction force microscopy on soft elastic substrates.

Dynamic Functional Connectivity between order and randomness and its evolution across the human adult lifespan.

Functional Connectivity (FC) during resting-state or task conditions is not static but inherently dynamic. Yet, there is no consensus on whether fluctuations in FC may resemble isolated transitions between discrete FC states rather than continuous changes. This quarrel hampers advancing the study of dynamic FC.

Confinement-Induced Transition between Wavelike Collective Cell Migration Modes.

The structural and functional organization of biological tissues relies on the intricate interplay between chemical and mechanical signaling. Whereas the role of constant and transient mechanical perturbations is generally accepted, several studies recently highlighted the existence of long-range mechanical excitations (i.e.

On the spatiotemporal regulation of cell tensional state.

Since the emergence of mechanobiology, mechanical signals have been shown to influence almost every process in biology. Cells transduce mechanical signals into biochemical signaling pathways, adjust their behavior and/or phenotype before transmitting these signals to neighboring cells. Mechanical signals thus appear as information, which can be "written" by cells in the surrounding extracellular matrix, "transmitted" through it and "read" by other cells.

Magneto-active substrates for local mechanical stimulation of living cells.

Cells are able to sense and react to their physical environment by translating a mechanical cue into an intracellular biochemical signal that triggers biological and mechanical responses. This process, called mechanotransduction, controls essential cellular functions such as proliferation and migration. The cellular response to an external mechanical stimulation has been investigated with various static and dynamic systems, so far limited to global deformations or to local stimulation through discrete substrates.

Multiscale Porosity Directs Bone Regeneration in Biphasic Calcium Phosphate Scaffolds.

Large and load-bearing bone defects are challenging to treat and cause pain and disfigurement. The design of efficacious bone scaffolds for the repair of such defects involves a range of length scales from the centimeter down to the micrometer-scale. Here, we assess the influence on bone regeneration of scaffold rod spacing (>300 μm) and microporosity (<50 μm), as well as the combination of different structures and materials in the same scaffold, i.

Quiescence of human muscle stem cells is favored by culture on natural biopolymeric films.

Background: Satellite cells are quiescent resident muscle stem cells that present an important potential to regenerate damaged tissue. However, this potential is diminished once they are removed from their niche environment in vivo, prohibiting the long-term study and genetic investigation of these cells. This study therefore aimed to provide a novel biomaterial platform for the in-vitro culture of human satellite cells that maintains their stem-like quiescent state, an important step for cell therapeutic studies.

Signal mingle: Micropatterns of BMP-2 and fibronectin on soft biopolymeric films regulate myoblast shape and SMAD signaling.

In vivo, bone morphogenetic protein 2 (BMP-2) exists both in solution and bound to the extracellular matrix (ECM). While these two modes of presentation are known to influence cell behavior distinctly, their role in the niche microenvironment and their functional relevance in the genesis of a biological response has sparsely been investigated at a cellular level. Here we used the natural affinity of BMP-2 for fibronectin (FN) to engineer cell-sized micropatterns of BMP-2.

Amyloid-like aggregates formation by blood plasma fibronectin.

Fibronectin (FN) is a multifunctional glycoprotein of the extracellular matrix (ECM) playing critical roles in physiological and pathological cell processes like adhesion, migration, growth, and differentiation. These various functions of FN are modulated by its supramolecular state. Indeed, FN can polymerize into different types of assemblies like fibrils and aggregates.

Beyond mice: Emerging and transdisciplinary models for the study of early-onset myopathies.

The use of the adapted models to decipher patho-physiological mechanisms of human diseases is always a great challenge. This is of particular importance for early-onset myopathies, in which pathological mutations often impact not only on muscle structure and function but also on developmental processes. Mice are currently the main animal model used to study neuromuscular disorders including the early-onset myopathies.

Stiffness-dependent cellular internalization of matrix-bound BMP-2 and its relation to Smad and non-Smad signaling.

Unlabelled: Surface coatings delivering BMP are a promising approach to render biomaterials osteoinductive. In contrast to soluble BMPs which can interact with their receptors at the dorsal side of the cell, BMPs presented as an insoluble cue physically bound to a biomimetic matrix, called here matrix-bound (bBMP-2), are presented to cells by their ventral side. To date, BMP-2 internalization and signaling studies in cell biology have always been performed by adding soluble (sBMP-2) to cells adhered on cell culture plates or glass slides, which will be considered here as a "reference" condition.

Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds.

Unlabelled: The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo.

Substrate Stiffness Combined with Hepatocyte Growth Factor Modulates Endothelial Cell Behavior.

Endothelial cells (ECs) play a crucial role in regulating various physiological and pathological processes. The behavior of ECs is modulated by physical (e.g.

Quick and easy microfabrication of T-shaped cantilevers to generate arrays of microtissues.

Over the past decade, a major effort was made to miniaturize engineered tissues, as to further improve the throughput of such approach. Most existing methods for generating microtissues thus rely on T-shaped cantilevers made by soft lithography and based on the use of negative SU-8 photoresist. However, photopatterning T-shaped microstructures with these negative photoresists is fastidious and time-consuming.

Construction and myogenic differentiation of 3D myoblast tissues fabricated by fibronectin-gelatin nanofilm coating.

In this study, we used a recently developed approach of coating the cells with fibronectin-gelatin nanofilms to build 3D skeletal muscle tissue models. We constructed the microtissues from C2C12 myoblasts and subsequently differentiated them to form muscle-like tissue. The thickness of the constructs could be successfully controlled by altering the number of seeded cells.

Differences in Morphology and Traction Generation of Cell Lines Representing Different Stages of Osteogenesis.

Osteogenesis is the process by which mesenchymal stem cells differentiate to osteoblasts and form bone. The morphology and root mean squared (RMS) traction of four cell types representing different stages of osteogenesis were quantified. Undifferentiated D1, differentiated D1, MC3T3-E1, and MLO-A5 cell types were evaluated using both automated image analysis of cells stained for F-actin and by traction force microscopy (TFM).

Spatio-Temporal Control of LbL Films for Biomedical Applications: From 2D to 3D.

Introduced in the '90s by Prof. Moehwald, Lvov, and Decher, the layer-by-layer (LbL) assembly of polyelectrolytes has become a popular technique to engineer various types of objects such as films, capsules and free standing membranes, with an unprecedented control at the nanometer and micrometer scales. The LbL technique allows to engineer biofunctional surface coatings, which may be dedicated to biomedical applications in vivo but also to fundamental studies and diagnosis in vitro.

Rigidity-patterned polyelectrolyte films to control myoblast cell adhesion and spatial organization.

, cells are sensitive to the stiffness of their micro-environment and especially to the spatial organization of the stiffness. studies of this phenomenon can help to better understand the mechanisms of the cell response to spatial variations of the matrix stiffness. In this work, we design polelyelectrolyte multilayer films made of poly(L-lysine) and a photo-reactive hyaluronan derivative.

Magnetic approaches to study collective three-dimensional cell mechanics in long-term cultures (invited).

Contractile forces generated by cells and the stiffness of the surrounding extracellular matrix are two central mechanical factors that regulate cell function. To characterize the dynamic evolution of these two mechanical parameters during tissue morphogenesis, we developed a magnetically actuated micro-mechanical testing system in which fibroblast-populated collagen microtissues formed spontaneously in arrays of microwells that each contains a pair of elastomeric microcantilevers. We characterized the magnetic actuation performance of this system and evaluated its capacity to support long-term cell culture.

Bio-functionalization of silicon carbide nanostructures for SiC nanowire-based sensors realization.

The bio-functionalization process consisting in grafting desoxyribo nucleic acid via aminopropyl-triethoxysilane is performed on several kinds of silicon carbide nanostructures. Prior, the organic layer is characterized on planar surface with fluorescence microscopy and X-ray photoelectron spectroscopy. Then, the functionalization is performed on two kinds of nanopillar arrays.

Microfabrication of a platform to measure and manipulate the mechanics of engineered microtissues.

Engineered tissues can be used to understand fundamental features of biology, develop organotypic in vitro model systems, and as engineered tissue constructs for replacing damaged tissue in vivo. However, a key limitation is an inability to test the wide range of parameters that might impact the engineered tissue in a high-throughput manner and in an environment that mimics the three-dimensional (3D) native architecture. We developed a microfabricated platform to generate arrays of microtissues embedded within 3D micropatterned matrices.

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

In this paper we report a fundamental morphological instability of constrained 3D microtissues induced by positive chemomechanical feedback between actomyosin-driven contraction and the mechanical stresses arising from the constraints. Using a 3D model for mechanotransduction we find that perturbations in the shape of contractile tissues grow in an unstable manner leading to formation of "necks" that lead to the failure of the tissue by narrowing and subsequent elongation. The magnitude of the instability is shown to be determined by the level of active contractile strain, the stiffness of the extracellular matrix, and the components of the tissue that act in parallel with the active component and the stiffness of the boundaries that constrain the tissue.