Extracellular Matrix News Volume 6.38 | Oct 1 2015

Integrins Activate Trimeric G Proteins via the Nonreceptor Protein GIV/Girdin
Scientists demonstrated that GIV enhances integrin-dependent cell responses upon extracellular matrix stimulation and makes tumor cells more invasive. These responses include remodeling of the actin cytoskeleton and PI3K-dependent signaling, resulting in enhanced haptotaxis and invasion. [J Cell Biol] Abstract

Contractility of Single Cardiomyocytes Differentiated from Pluripotent Stem Cells Depends on Physiological Shape and Substrate Stiffness
Investigators analyzed the effects of cell shape and substrate stiffness on the shortening and movement of labeled sarcomeres and the translation of sarcomere activity to mechanical output (contractility) in live engineered cardiomyocytes differentiated from human pluripotent stem cells. [Proc Natl Acad Sci USA] Abstract | Press Release

Matrix Metalloproteinase 14 Is Required for Fibrous Tissue Expansion
Researchers showed that tendon development is arrested in Scleraxis-Cre::Mmp14 lox/lox mice that are unable to release collagen fibrils from plasma membrane fibripositors. In contrast to its role in collagen turnover in adult tissue, MMP14 promotes embryonic tissue formation by releasing collagen fibrils from the cell surface. [eLife] Abstract | Full Article

Integrin-Specific Hydrogels as Adaptable Tumor Organoids for Malignant B and T Cells
Scientists engineered adaptable three-dimensional tumor organoids presenting adhesive peptides with distinct integrin specificities to B and T cell lymphoma cells that resulted in enhanced proliferation, clustering, and drug resistance to the chemotherapeutics and a new class of histone deacetylase inhibitor, Panobinostat. [Biomaterials] Abstract

Osteogenic Differentiation Evaluation of an Engineered Extracellular Matrix Based Tissue Sheet for Potential Periosteum Replacement
Researchers investigated if the natural extracellular matrix (ECM) sheet and the substrate alignment could promote in vitro osteogenesis of human mesenchymal stem cells. The conventional cell culture substrates collagen I-coated polydimethylsiloxane and tissue culture plastic were used as controls. [ACS Appl Mater Interfaces] Abstract

The Insulin Response Integrates Increased TGF-β Signaling through Akt-Induced Enhancement of Cell Surface Delivery of TGF-β Receptors
Investigators found that Akt-mediated phosphorylation of AS160, a RabGAP [guanosine triphosphatase (GTPase)–activating protein], promoted the translocation of transforming growth factor–β (TGF-β) receptors from intracellular stores to the plasma membrane of mouse embryonic fibroblasts and NMuMG epithelial cells. [Sci Signal] Abstract

Brain Extracellular Matrix Retains Connectivity in Neuronal Networks
Researchers investigated the role of the extracellular matrix (ECM) in the regulation of the network activity in dissociated hippocampal cultures grown on microelectrode arrays. They found that enzymatic removal of the ECM in mature cultures led to transient enhancement of neuronal activity, but prevented disinhibition-induced hyperexcitability that was evident in age-matched control cultures with intact ECM. [Sci Rep] Full Article

Three-Dimensional Matrix Fiber Alignment Modulates Cell Migration and MT1-MMP Utility by Spatially and Temporally Directing Protrusions
The authors present an integrated, quantitative study of parameters—including pore size, crosslink density, structural organization, and stiffness—across a broad range of complex matrix configurations using self-assembling three-dimensional collagen and show how each parameter relates to the others and to cell motility. [Sci Rep] Full Article

Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix for In Vitro Irritation Testing
Scientists investigated the use of acellular porcine peritoneum extracellular matrix as a substrate to construct full-thickness human skin equivalents for use as an irritation screening tool. The acellular peritoneum matrix exhibited excellent skin cell attachment and proliferation for human dermal fibroblasts and immortalized human keratinocytes. [Tissue Eng Part A] Abstract

Fibrinolytic PLGA Nanoparticles for Slow Clot Lysis within Abdominal Aortic Aneurysms Attenuate Proteolytic Loss of Vascular Elastic Matrix
Scientists investigated the ability of tissue plasminogen activator released from poly(lactic-co-glycolic acid) (PLGA) nanoparticles to slowly lyse fibrin clots without inducing proteolytic injury and matrix synthesis-inhibitory effects on cultured rat aneurysmal smooth muscle cells. [Mater Sci Eng C-Mater Biol Appl]
Abstract | Graphical Abstract

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Cornell Dots Research Collaboration Leads to $10 Million Cancer Center
Cornell University, in partnership with Memorial Sloan Kettering Cancer Center, is opening a new $10 million Center of Cancer Nanotechnology Excellence that brings together scientists, engineers, biologists and physicians to develop and translate new cancer care applications based on nanotechnology. [Cornell University] Press Release

Postdoctoral Fellow Albert Kim Receives First Hearst Fellowship for Stem Cell Research
How do you turn stem cells into nephrons, the functional unit of the kidney? Albert D. Kim, a postdoctoral fellow in the laboratory of Andy McMahon, is exploring this question with support from a Hearst Fellowship, an award recognizing an exceptional junior postdoctoral fellow pursuing stem cell research at USC. [Keck School of Medicine of USC] Press Release

Building Human Breast Tissue, Cell by Cell
The next frontier in developing therapies for cancer and other diseases could come through studying organ development or tumor growth in living humans. Problem is, there’s no ethical way of doing that using current technology. Zev Gartner, PhD, has focused on the next best thing: his lab is building fully functioning 3-D human tissue, cell by cell. [University of California, San Francisco] Press Release

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NEW Director – Clinical Development (Novadip Biosciences)

NEW Postdoctoral Position – Mechanisms of Leukocyte Extravasation (University Hospital of Münster)

Assistant Professor – Stem Cell Biology (University of South Carolina)

Junior Faculty Position – Bioengineering (Stanford University)

Assistant Professor – Stem Cell Biology (Stanford University)

Postdoctoral Fellowships – Embryonic Stem Cells, Bio-NEMS, Tissue Engineering (University of South Carolina)

PhD Position – Materials Engineering (IFP Energies Nouvelles)

Postdoctoral Research Fellow – Ex Vivo Tumor Organoid Models (Fred Hutchinson Cancer Research Center)

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