Extracellular Matrix News Volume 8.06 | Feb 16 2017

TOP STORY

Modeling the Two-Way Feedback between Contractility and Matrix Realignment Reveals a Nonlinear Mode of Cancer Cell Invasion

Researchers incorporated a mechanochemical free-energy–based approach to elucidate how the two-way feedback loop between cell contractility and matrix fiber realignment and strain stiffening enables the cells to polarize and develop contractile forces to break free from the tumor spheroids and invade into the extracellular matrix. [Proc Natl Acad Sci USA] Abstract

(Ranked by impact factor of the journal)

Intrinsically Disordered Proteins Drive Enamel Formation via an Evolutionarily Conserved Self-Assembly Motif

Using targeted mutations in mice and high-resolution imaging, investigators showed that impairment of ameloblastin self-assembly causes disorganization of the enamel organic matrix and yields enamel with disordered hydroxyapatite crystallites. [Proc Natl Acad Sci USA] Abstract

Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases

The authors showed how differential expression of a network of extracellular matrix molecules and their interacting proteins contributes to risk of relapse in distinct latent lung adenocarcinoma (LUAD) subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis. [Cancer Res] Abstract | Full Article | Press Release

Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, researchers hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. [Cell Rep] Full Article | Graphical Abstract

Extracellular Protonation Modulates Cell-Cell Interaction Mechanics and Tissue Invasion in Human Melanoma Cells

The authors tested the modulation of cell-cell-adhesion by extracellular pH and NHE1. MV3 tumor spheroids embedded in a collagen matrix unraveled the efficacy of cell-cell contact loosening and 3D emigration into an environment mimicking physiological confinement. [Sci Rep] Full Article

Three-Dimensional Collagen Matrix Induces a Mechanosensitive Invasive Epithelial Phenotype

Scientists used a 3D epithelial morphogenesis model in which cells were cultured in biochemically and mechanically defined matrices to examine matrix-mediated gene expression and the associated phenotypic response. They found that 3D collagen matrix promoted expression of mesenchymal genes including MT1-MMP, which was required for collagen-stimulated invasive behavior. [Sci Rep] Full Article

The Binding Capacity of α1β1-, α2β1- and α10β1-Integrins Depends on Non-Collagenous Surface Macromolecules Rather than the Collagens in Cartilage Fibrils

Investigators showed that chondrocytes strongly bind to cartilage collagens in the form of individual triple helical molecules but very weakly to fibrils formed by the same molecules. They also found that chondrocyte integrins α1β1-, α2β1- and α10β1-integrins and their I-domains have the same characteristics. [Matrix Biol] Abstract

Hydrogen Sulfide Inhibits High Glucose-Induced NADPH Oxidase 4 Expression and Matrix Increment by Recruiting Inducible Nitric Oxide Synthase in the Kidney Proximal Tubular Epithelial Cells

Since hydrogen sulfide (H₂S) inhibits high glucose-induced matrix protein increment by activating AMPK in renal cells, investigators examined if H₂S inhibits high glucose induced expression of NOX4 and matrix protein and if H₂S nitric oxide pathways are integrated. High glucose increased NOX4 expression and activity at 24 hours in renal proximal tubular epithelial cells that was inhibited by sodium hydrosulfide, a source of H₂S. [J Biol Chem] Abstract | Full Article

Human Th17 Migration in Three-Dimensional Collagen Involves p38 MAPK

Scientists examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen. Using specific inhibitor and siRNA, they found that p38 is necessary for human Th17 migration in three-dimensional (3D) collagen and that 3D collagen increases p38 phosphorylation. [J Cell Biochem] Abstract

Simvastatin Inhibits IL-1β-Induced Apoptosis and Extracellular Matrix Degradation by Suppressing the NF-kB and MAPK Pathways in Nucleus Pulposus Cells

Researchers investigated the mechanism underlying the effect of simvastatin on intervertebral disk degeneration (IDD). The viability of nucleus pulposus (NP) cells was determined by the methyl-thiazolyl-tetrazolium assay. The apoptosis of NP cells was measured by flow cytometric analysis, terminal deoxynucleotidyl transferase dUTP nick end labeling, and western blotting of relevant apoptotic proteins. [Inflammation] Abstract

A Review of Gradient Stiffness Hydrogels Used in Tissue Engineering and Regenerative Medicine

Given the importance of gradient stiffness hydrogels in basic research and biomedical applications, there is a clear need for systems for gradient stiffness hydrogel design strategies and their applications. The authors highlight past work in the field of gradient stiffness hydrogels fabrication methods, mechanical property test, applications as well as areas for future study. [J Biomed Mater Res A] Abstract

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

SpinalCyte, LLC Announces New U.S. Patent

SpinalCyte, LLC announced the issuance of U.S. Patent No. 9,545,432, “Methods and Compositions for Repair of Cartilage Using an In Vivo Bioreactor.” [SpinalCyte, LLC] Press Release

Chi-Med Initiates First-in-Human Clinical Trial of Novel FGFR Inhibitor HMPL-453 in Australia

Hutchison China MediTech Limited (Chi-Med) announces that it has initiated the first-in-human Phase I clinical trial of HMPL-453 in Australia. HMPL-453 is a novel, highly selective and potent small molecule inhibitor targeting fibroblast growth factor receptor. [Hutchison China MediTech Limited] Press Release

Verastem Announces Dosing of First Patient in Combination Trial of Defactinib and Avelumab in Patients with Ovarian Cancer

Verastem, Inc. announced dosing of the first patient in a new clinical trial evaluating avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in combination with Verastem’s defactinib, an investigational focal adhesion kinase inhibitor, in patients with advanced ovarian cancer. [Verastem, Inc.] Press Release

Broad Institute Wins Bitter Battle over CRISPR Patents

A panel of US Patent and Trademark Office judges have determined that a series of patents granted for CRISPR-Cas9 gene editing to the Broad Institute of MIT and Harvard will stand. [Nature News] Editorial

Henrietta Lacks’s Family Wants Compensation for Her Cells

The eldest son of Henrietta Lacks wants compensation from Johns Hopkins University and possibly others for the unauthorized use of her cells in research that led to decades of medical advances. The cells taken from the 31-year-old after she died of an aggressive form of cervical cancer in 1951 were the first to live outside the body in a glass tube. [The Washington Post] Editorial

NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
May 11-13, 2017
Heidelberg, Germany

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Role of Extracellular Matrix Proteolysis (University of California, San Francisco)

NEW Assistant/Associate Professor – Various Projects (University of Missouri Biomedical Sciences)

PhD Position – Molecular Studies of Bacterial Amyloid Secretion (VIB-VUB Center for Structural Biology)

Postdoctoral Fellow/Research Scientist – Cell-Extracellular Matrix Interactions (University of Michigan)

Professor – Molecular Biochemistry (University of Oulu)

Faculty Positions – Medical Research (Pontificia Universidad Católica de Chile)

PhD Studentship/Postdoctoral Fellow – Design and Fabrication of Clinically Relevant Polymer-Based Stents for Chronic Rhinosinusitis (University of Gent and Free University Brussels)

Postdoctoral Fellow – Studying the Forms and Activity of Extracellular Tau (Brigham & Women’s Hospital)

PhD Studentship – Light-Addressable Neuroactive Matrices (KU Leuven)

Postdoctoral Scientist – Various Projects (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Nanocellulose Fibril Characterization for New Materials (KTH Royal Institute of Technology)

Tenure Track Faculty Position – Kidney Bench Research (University of Pennsylvania)

Faculty Positions – Department of Biomedical Engineering (Southern University of Science and Technology)

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