Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling.

Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs).

Quantitative atlas of collagen hydrogels reveals mesenchymal cancer cell traction adaptation to the matrix nanoarchitecture.

Collagen-based hydrogels are commonly used in mechanobiology to mimic the extracellular matrix. A quantitative analysis of the influence of collagen concentration and properties on the structure and mechanics of the hydrogels is essential for tailored design adjustments for specific in vitro conditions. We combined focused ion beam scanning electron microscopy and rheology to provide a detailed quantitative atlas of the mechanical and nanoscale three-dimensional structural alterations that occur when manipulating different hydrogel's physicochemistry.

A Spontaneous In Situ Thiol-Ene Crosslinking Hydrogel with Thermo-Responsive Mechanical Properties.

The thermo-responsive behavior of Poly(N-isopropylacrylamide) makes it an ideal candidate to easily embed cells and allows the polymer mixture to be injected. However, P(NiPAAm) hydrogels possess minor mechanical properties. To increase the mechanical properties, a covalent bond is introduced into the P(NIPAAm) network through a biocompatible thiol-ene click-reaction by mixing two polymer solutions.

DLC1 promotes mechanotransductive feedback for YAP via RhoGAP-mediated focal adhesion turnover.

Angiogenesis is a tightly controlled dynamic process demanding a delicate equilibrium between pro-angiogenic signals and factors that promote vascular stability. The spatiotemporal activation of the transcriptional co-factors YAP (herein referring to YAP1) and TAZ (also known WWTR1), collectively denoted YAP/TAZ, is crucial to allow for efficient collective endothelial migration in angiogenesis. The focal adhesion protein deleted-in-liver-cancer-1 (DLC1) was recently described as a transcriptional downstream target of YAP/TAZ in endothelial cells.

SGABU computational platform for multiscale modeling: Bridging the gap between education and research.

Background And Objective: In accordance with the latest aspirations in the field of bioengineering, there is a need to create a web accessible, but powerful cloud computational platform that combines datasets and multiscale models related to bone modeling, cancer, cardiovascular diseases and tissue engineering. The SGABU platform may become a powerful information system for research and education that can integrate data, extract information, and facilitate knowledge exchange with the goal of creating and developing appropriate computing pipelines to provide accurate and comprehensive biological information from the molecular to organ level.

Methods: The datasets integrated into the platform are obtained from experimental and/or clinical studies and are mainly in tabular or image file format, including metadata.

Synthetic fibrous hydrogels as a platform to decipher cell-matrix mechanical interactions.

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood.

Mechanical properties-translucency-microstructure relationships in commercial monolayer and multilayer monolithic zirconia ceramics.

Objectives: To evaluate the phase composition, microstructure, optical properties and mechanical properties of eight commercially available multilayer and monolayer monolithic dental zirconias.

Methods: Five commercial 3Y-TZP (GC ST, GC HT [GC, Tokyo Japan]; Katana ML, Katana HT [Kuraray Noritake] and Lava Plus [3M Oral Care]) and three Y-PSZ (Katana STML, Katana UTML [Kuraray Noritake]; GC UHT [GC, Tokyo Japan]) zirconia ceramic grades were cut in plate-shaped specimens, sintered according to the manufacturer's instructions and mirror polished. The zirconia chemical composition was determined using X-ray fluorescence (XRF), phase composition was characterized using X-ray diffraction (XRD), while the grain size was measured using scanning electron microscopy (SEM).

Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the gene was identified as the causative mutation of FOP in 2006.

CCM2-deficient endothelial cells undergo a ROCK-dependent reprogramming into senescence-associated secretory phenotype.

Cerebral cavernous malformation (CCM) is a cerebrovascular disease in which stacks of dilated haemorrhagic capillaries form focally in the brain. Whether and how defective mechanotransduction, cellular mosaicism and inflammation interplay to sustain the progression of CCM disease is unknown. Here, we reveal that CCM1- and CCM2-silenced endothelial cells expanded in vitro enter into senescence-associated secretory phenotype (SASP) that they use to invade the extracellular matrix and attract surrounding wild-type endothelial and immune cells.

Actuation enhances patterning in human neural tube organoids.

Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here, we develop devices that enable the actuation of organoids.

Chlorite oxidized oxyamylose differentially influences the microstructure of fibrin and self assembling peptide hydrogels as well as dental pulp stem cell behavior.

Tailored hydrogels mimicking the native extracellular environment could help overcome the high variability in outcomes within regenerative endodontics. This study aimed to evaluate the effect of the chemokine-binding and antimicrobial polymer, chlorite-oxidized oxyamylose (COAM), on the microstructural properties of fibrin and self-assembling peptide (SAP) hydrogels. A further goal was to assess the influence of the microstructural differences between the hydrogels on the in vitro behavior of human dental pulp stem cells (hDPSCs).

Patterned dextran ester films as a tailorable cell culture platform.

The elucidation of cell-surface interactions and the development of model platforms to help uncover their underlying mechanisms remains vital to the design of effective biomaterials. To this end, dextran palmitates with varying degrees of substitution were synthesised with a multipurpose functionality: an ability to modulate surface energy through surface chemistry, and an ideal thermal behaviour for patterning. Herein, dextran palmitate films are produced by spin coating, and patterned by thermal nanoimprint lithography with nano-to-microscale topographies.

Simulating flow induced migration in vascular remodelling.

Shear stress induces directed endothelial cell (EC) migration in blood vessels leading to vessel diameter increase and induction of vascular maturation. Other factors, such as EC elongation and interaction between ECs and non-vascular areas are also important. Computational models have previously been used to study collective cell migration.

Intercellular Adhesion Stiffness Moderates Cell Decoupling as a Function of Substrate Stiffness.

The interplay between cell-cell and cell-substrate interactions is complex yet necessary for the formation and healthy functioning of tissues. The same mechanosensing mechanisms used by the cell to sense its extracellular matrix also play a role in intercellular interactions. We used the discrete element method to develop a computational model of a deformable cell that includes subcellular components responsible for mechanosensing.

Actomyosin-dependent invasion of endothelial sprouts in collagen.

During sprouting angiogenesis-the growth of blood vessels from the existing vasculature-endothelial cells (ECs) adopt an elongated invasive form and exert forces at cell-cell and cell-matrix interaction sites. These cell shape changes and cellular tractions require extensive reorganizations of the actomyosin network. However, the respective roles of actin and myosin for endothelial sprouting are not fully elucidated.

Modeling of Mechanosensing Mechanisms Reveals Distinct Cell Migration Modes to Emerge From Combinations of Substrate Stiffness and Adhesion Receptor-Ligand Affinity.

Mesenchymal cell migration is an integral process in development and healing. The process is regulated by both mechanical and biochemical properties. Mechanical properties of the environment are sensed through mechanosensing, which consists of molecular responses mediated by mechanical signals.

Lipid availability determines fate of skeletal progenitor cells via SOX9.

The avascular nature of cartilage makes it a unique tissue, but whether and how the absence of nutrient supply regulates chondrogenesis remain unknown. Here we show that obstruction of vascular invasion during bone healing favours chondrogenic over osteogenic differentiation of skeletal progenitor cells. Unexpectedly, this process is driven by a decreased availability of extracellular lipids.

Matrix deformations around angiogenic sprouts correlate to sprout dynamics and suggest pulling activity.

Angiogenesis is the formation of new blood vessels from the pre-existing vasculature. It is essential for normal tissue growth and regeneration, and also plays a key role in many diseases [Carmeliet in Nat Med 9:653-660, 2003]. Cytoskeletal components have been shown to be important for angiogenic sprout initiation and maintenance [Kniazeva and Putnam in Am J Physiol 297:C179-C187, 2009] as well as endothelial cell shape control during invasion [Elliott et al.

The role of actin protrusion dynamics in cell migration through a degradable viscoelastic extracellular matrix: Insights from a computational model.

Actin protrusion dynamics plays an important role in the regulation of three-dimensional (3D) cell migration. Cells form protrusions that adhere to the surrounding extracellular matrix (ECM), mechanically probe the ECM and contract in order to displace the cell body. This results in cell migration that can be directed by the mechanical anisotropy of the ECM.

Effect of ultrasound on bone fracture healing: A computational mechanobioregulatory model.

Bone healing process is a complicated phenomenon regulated by biochemical and mechanical signals. Experimental studies have shown that ultrasound (US) accelerates bone ossification and has a multiple influence on cell differentiation and angiogenesis. In a recent work of the authors, a bioregulatory model for providing bone-healing predictions was addressed, taking into account for the first time the salutary effect of US on the involved angiogenesis.

Polysaccharides for tissue engineering: Current landscape and future prospects.

Biological studies on the importance of carbohydrate moieties in tissue engineering have incited a growing interest in the application of polysaccharides as scaffolds over the past two decades. This review provides a perspective of the recent approaches in developing polysaccharide scaffolds, with a focus on their chemical modification, structural versatility, and biological applicability. The current major limitations are assessed, including structural reproducibility, the narrow scope of polysaccharide modifications being applied, and the effective replication of the extracellular environment.

Spatiotemporal Analyses of Cellular Tractions Describe Subcellular Effect of Substrate Stiffness and Coating.

Cells interplay with their environment through mechanical and chemical interactions. To characterize this interplay, endothelial cells were cultured on polyacrylamide hydrogels of varying stiffness, coated with either fibronectin or collagen. We developed a novel analysis technique, complementary to traction force microscopy, to characterize the spatiotemporal evolution of cellular tractions: We identified subpopulations of tractions, termed traction foci, and tracked their magnitude and lifetime.

Combustion-derived particles inhibit in vitro human lung fibroblast-mediated matrix remodeling.

Background: The continuously growing human exposure to combustion-derived particles (CDPs) drives in depth investigation of the involved complex toxicological mechanisms of those particles. The current study evaluated the hypothesis that CDPs could affect cell-induced remodeling of the extracellular matrix due to their underlying toxicological mechanisms. The effects of two ultrafine and one fine form of CDPs on human lung fibroblasts (MRC-5 cell line) were investigated, both in 2D cell culture and in 3D collagen type I hydrogels.