Extracellular Matrix News Volume 8.14 | Apr 13 2017

TOP STORY

Anisotropic Forces from Spatially Constrained Focal Adhesions Mediate Contact Guidance Directed Cell Migration

The authors demonstrated that for single cells, aligned architectures providing contact guidance cues induce constrained focal adhesion maturation and associated F-actin alignment, consequently orchestrating anisotropic traction stresses that drive cell orientation and directional migration. [Nat Commun] Full Article

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Cell-Matrix Adhesion and Cell-Cell Adhesion Differentially Control Basal Myosin Oscillation and Drosophila Egg Chamber Elongation

Researchers demonstrated that cell–matrix adhesion positively regulates basal junctional Rho1 activity and medio-basal ROCK and myosin activities, thus strongly controlling tissue elongation. Differently, cell–cell adhesion governs basal myosin oscillation through controlling medio-basal distributions of both ROCK and myosin signals, which are related to the spatial limitations of cell–matrix adhesion and stress fibers. [Nat Commun] Full Article

Plasma Fibronectin Stabilizes Borrelia burgdorferi–Endothelial Interactions under Vascular Shear Stress by a Catch-Bond Mechanism

Scientists investigated how B. burgdorferi exploits fibronectin (Fn) to interact with endothelia under physiological shear stress, using recently developed live cell imaging and particle-tracking methods for studying bacterial–endothelial interaction biomechanics. They found that B. burgdorferi does not primarily target insoluble matrix Fn deposited on endothelial surfaces but, instead, recruits and induces polymerization of soluble plasma Fn, an abundant protein in blood plasma that is normally soluble and nonadhesive. [Proc Natl Acad Sci USA] Full Article

Extracellular Matrix/Integrin Signaling Promotes Resistance to Combined Inhibition of HER2 and PI3K in HER2⁺ Breast Cancer

Investigators identified mechanisms of resistance to combined inhibition of HER2 and PI3K. RNA-sequencing of trastuzumab, pertuzumab and buparlisib-resistant tumors revealed that extracellular matrix and cell adhesion genes, including collagen II, were markedly upregulated, accompanied by activation of integrin β1/Src. [Cancer Res] Abstract

YAP-Mediated Mechanotransduction Determines the Podocyte’s Response to Damage

Scientists showed that podocyte injury stimulated the activity of the transcriptional coactivator YAP and the expression of YAP target genes in a rat model of glomerular disease before the development of proteinuria. YAP overexpression in cultured podocytes increased the abundance of extracellular matrix–related proteins that can contribute to fibrosis. [Sci Signal] Abstract

Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke

Investigators constructed hypoxia response element (HRE)-regulated matrix metalloproteinase 9 (MMP-9) to explore its effect on glial scars and neurogenesis in delayed ischemic stroke. They found that HRE-MMP-9 improved neurological outcomes, reduced ischemia-induced brain atrophy, and degraded glial scars. [Mol Ther] Full Article

Oxidation of KCNB1 Potassium Channels Triggers Apoptotic Integrin Signaling in the Brain

Scientists showed that the apoptotic signal originates from integrins, which form macromolecular complexes with KCNB1 channels. The initial stimulus is transduced to Fyn and possibly other Src family members by focal adhesion kinase. Thus KCNB1 and integrin alpha chain V coimmunoprecipitated in the mouse brain and these interactions were retained upon channel’s oxidation. [Cell Death Dis] Full Article

Extracellular Cystatin SN and Cathepsin B Prevent Cellular Senescence by Inhibiting Abnormal Glycogen Accumulation

The authors observed that the knockdown of cystatin SN induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells. [Cell Death Dis] Full Article

Knockdown of Stem Cell Regulator Oct4A in Ovarian Cancer Reveals Cellular Reprogramming Associated with Key Regulators of Cytoskeleton-Extracellular Matrix Remodeling

Investigators demonstrated key roles for Oct4A in tumor cell survival, metastasis and chemoresistance in in vitro and in vivo models of ovarian cancer. Across all preparations of HEY Oct4A KD samples significant alterations in protein networks associated with cytoskeleton, extracellular matrix, proliferation, adhesion, metabolism, epithelial-mesenchymal transition, cancer stem cells and drug resistance was observed. [Sci Rep] Full Article

Rationally Designed Ligand-Independent Peptide Inhibitors of TREM-1 Ameliorate Collagen-Induced Arthritis

Researchers evaluated the anti-arthritic activity of a novel, ligand-independent triggering receptor expressed on myeloid cells 1 (TREM-1) inhibitory nonapeptide GF9 that was rationally designed using the signaling chain homo oligomerization model of cell signaling. They showed that GF9, but not control peptide, ameliorated CIA and protected against bone and cartilage damage. [J Cell Mol Med] Full Article

Multiple Roles of Integrin-α3 at the Neuromuscular Junction

Using genetically modified mice, scientists found that integrin-α3, an adhesion receptor at the presynaptic membrane, is involved in the localization of active zone components and efficient synaptic vesicle release. Integrin-α3 also regulates integrity of the synapse: mutant neuromuscular junctions present with progressive structural changes and upregulated autophagy, features commonly observed during aging and in models of neurodegeneration. [J Cell Sci] Abstract | Full Article

Emerging Biofabrication Strategies for Engineering Complex Tissue Constructs

The authors highlight recent work on emerging three-dimensional bioprinting and textile techniques, compare the advantages and shortcomings of these approaches, outline the use of common biomaterials and advanced hybrid scaffolds, and describe several design considerations including the structural, physical, biological, and economical parameters that are crucial for the fabrication of functional, complex, engineered tissues. [Adv Mater] Abstract

MMP-2 and 9 in Chronic Kidney Disease

Gelatinases are members of the matrix metalloproteinase (MMPs) family; they play an important role in the degradation of the extracellular matrix. This effect is also crucial in the development and progression of chronic kidney disease. Its expression, as well as its activity regulation are closely related to the cell signaling pathways, hypoxia and cell membrane structural change. With the in-depth understanding about the function of gelatinases, a more specific and accurate understanding of their role in the human body could be garnered. [Int J Mol Sci] Full Article

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American Heart Association and the Paul G. Allen Frontiers Group Join Forces to Support Two $1.5 Million Grants for Pioneering Cardiovascular Researchers

Shedding light on the unknown role of the extracellular matrix in heart health and disease is the focus of an innovative collaboration between the American Heart Association, the world’s leading voluntary health organization devoted to fighting cardiovascular disease, and The Paul G. Allen Frontiers Group. There will be two significant grants of $1.5 million each for pioneering researchers to make strides toward solving cardiovascular disease. [Allen Institute] Press Release

$2.4 Million National Eye Institute Grant to JAX for Retinal Pigment Epithelium Studies

The National Eye Institute has awarded Jackson Laboratory (JAX) Professor Patsy Nishina, Ph.D., and Associate Professor Gregory Carter, Ph.D., a four-year grant totaling $2,414,304 to study diseases of the retinal pigment epithelium, with the goal of identifying druggable targets for age-related macular degeneration and other heritable retinal diseases. [The Jackson Laboratory] Press Release

FDA Signs Collaborative Agreement with Emulate, Inc. to Use Organs-on-Chips Technology as a Toxicology Testing Platform for Understanding How Products Affect Human Health and Safety

Emulate, Inc. announced that it has entered into a Cooperative Research and Development Agreement with the U.S. Food and Drug Administration’s (FDA) Office of Foods and Veterinary Medicine. The system recreates the natural physiology of specific human tissues and organs, and is designed to provide a predictive model of human response to diseases, medicines, chemicals, and foods with greater precision and detail than other preclinical testing methods, such as cell culture or animal-based experimental testing. [Emulate, Inc.] Press Release | Editorial

Joining the European Union Leads to Less Cross-Border Collaboration

When the European Union expanded in the 2000s, it had a negative impact on scientific collaborations between researchers in new member countries and elsewhere, a study has found. [Nature News] Editorial

U.S. Report Calls for Research Integrity Board

The U.S. research community needs to do a better job of both investigating misconduct allegations and promoting ethical conduct—or the government might act unilaterally in ways that scientists won’t like. That’s the implicit message sent by a new report out from the National Academies of Science, Engineering, and Medicine entitled Fostering Integrity in Research. [ScienceInsider] Editorial

Review of Canadian Science Calls for Better Oversight, Coordination — and More Money

To reinvigorate its science base, Canada needs to “reinvest” almost CAD $500 million in basic, investigator-led research over the next four years, according to a long-awaited review of the country’s science and innovation landscape. [ScienceInsider] Editorial

NEW Mechanical Forces in Biology
July 12-15, 2017
Heidelberg, Germany

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NEW Research Fellow – Functional Roles of Stem Cell Derived Extracellular Vesicles (Mayo Clinic)

NEW Postdoctoral Fellow – Scarring (SUNY Upstate Medical Center)

Postdoctoral Position – Organic Bioelectronics (Northwestern University)

PhD – Microsystems Technology with a Focus on Biomaterials-on-Chip (Uppsala Universitet)

Postdoctoral Scientist – Quantitative Biology of Cell Fate and Tissue Dynamics (University of Oxford)

Professors/Associate Professors/Assistant Professors – Tissue Engineering and Regenerative Medicine (The Chinese University of Hong Kong)

Open Rank Professor – Materials Science and Engineering (The Pennsylvania State University)

Postdoctoral Fellowship – Cardiac Cell Membrane Expression of Ion Channels (UMR_S1166-Cardiovascular diseases, Metabolism and Nutriomics Research Unit)

Professors/Associate Professors/Assistant Professors (The Chinese University of Hong Kong)

Postdoctoral Fellow – Decorin and Perlecan and Their Effects on Tumor Angiogenesis, Autophagy, and Mitophagy (Thomas Jefferson University and Jefferson Health)

Postdoctoral Fellow – Cellular Mechanobiology (University of Buffalo)

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