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Cellular and Molecular Bioengineering

James R Wodicka, Vasilios A Morikis, Tima Dehghani, Scott I Simon, Alyssa Panitch
Introduction: The glycocalyx is a layer of glycoproteins, proteoglycans and glycosaminoglycans that coats the luminal surface of most blood vessels. It effectively regulates adhesive interactions between leukocytes in flowing blood and the endothelium, where during inflammation, binding to E- and P-selectins and intercellular adhesion molecule-1 (ICAM-1) promotes cell tethering and arrest under shear flow. Methods: In this study, we examine the targeting of E-selectin by an engineered peptide moiety bound to a dermatan sulfate backbone...
2019: Cellular and Molecular Bioengineering
M S Valentine, P A Link, J A Herbert, F Kamga Gninzeko, M B Schneck, K Shankar, J Nkwocha, A M Reynolds, R L Heise
Introduction: Ventilator-Induced lung injury (VILI) is a form of acute lung injury that is initiated or exacerbated by mechanical ventilation. The aging lung is also more susceptible to injury. Harmful mechanical stretch of the alveolar epithelium is a recognized mechanism of VILI, yet little is known about how mechanical stretch affects aged epithelial cells. Disruption to Endoplasmic Reticulum (ER) homeostasis results in a condition known as ER stress that leads to disruption of cellular homeostasis, apoptosis, and inflammation...
December 2018: Cellular and Molecular Bioengineering
Joshua T Morgan, Wade G Stewart, Robert A McKee, Jason P Gleghorn
Introduction –: Clinical observations and animal models suggest a critical role for the dynamic regulation of transmural pressure and peristaltic airway smooth muscle contractions for proper lung development. However, it is currently unclear how such mechanical signals are transduced into molecular and transcriptional changes at the cell level. To connect these physical findings to a mechanotransduction mechanism, we identified a known mechanosensor, TRPV4, as a component of this pathway...
October 2018: Cellular and Molecular Bioengineering
Weiyu Zhao, Chengxiang Zhang, Bin Li, Xinfu Zhang, Xiao Luo, Chunxi Zeng, Wenqing Li, Min Gao, Yizhou Dong
Introduction: In the past decade, messenger RNA (mRNA) has been extensively explored in a wide variety of biomedical applications. However, efficient delivery of mRNA is still one of the key challenges for its broad applications in the clinic. Recently, lipid polymer hybrid nanoparticles (LPNs) are evolving as a promising class of biomaterials for RNA delivery, which integrate the physicochemical properties of both lipids and polymers. We previously developed an N1 ,N3 ,N5-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT) derived lipid-like nanomaterial (TT3-LLN) which was capable of effectively delivering multiple types of mRNA...
October 2018: Cellular and Molecular Bioengineering
Ritu Goyal, Chintan H Kapadia, Jilian R Melamed, Rachel S Riley, Emily S Day
Introduction: MicroRNAs (miRNAs) are short noncoding RNAs whose ability to regulate the expression of multiple genes makes them potentially exciting tools to treat disease. Unfortunately, miRNAs cannot passively enter cells due to their hydrophilicity and negative charge. Here, we report the development of layer-by-layer assembled nanoshells (LbL-NS) as vehicles for efficient intracellular miRNA delivery. Specifically, we developed LbL-NS to deliver the tumor suppressor miR-34a into triple-negative breast cancer (TNBC) cells, and demonstrate that these constructs can safely and effectively regulate the expression of SIRT1 and Bcl-2, two known targets of miR-34a, to decrease cell proliferation...
October 2018: Cellular and Molecular Bioengineering
Michael R King, William E Bentley, Lola Eniola-Adefeso
No abstract text is available yet for this article.
October 2018: Cellular and Molecular Bioengineering
Charlotte E Vorwald, Kaitlin C Murphy, J Kent Leach
Introduction: Diabetes is an emerging epidemic in the developing world and represents a major risk factor for cardiovascular disease. Among other issues, patients with diabetes suffer from diminished endothelial cell (EC) function, which contributes to impaired vasculogenesis and recovery from ischemic insult. The formation of cells into three-dimensional spheroids promotes cell survival and activates key signaling pathways through the upregulation of cell-cell contacts, providing an opportunity to overcome shortcomings associated with individual autologous cells...
August 2018: Cellular and Molecular Bioengineering
Mark J Golob, Dawiyat Massoudi, Diana M Tabima, James L Johnston, Gregory D Wolf, Timothy A Hacker, Daniel S Greenspan, Naomi C Chesler
Introduction: Bone morphogenetic protein 1 (BMP1) is part of an extracellular metalloproteinase family that biosynthetically processes procollagen molecules. BMP1- and tolloid-like (TLL1) proteinases mediate the cleavage of carboxyl peptides from procollagen molecules, which is a crucial step in fibrillar collagen synthesis. Ablating the genes that encode BMP1-related proteinases ( Bmp1 and Tll1 ) post-natally results in brittle bones, periodontal defects, and thin skin in conditional knockout (BTKO ) mice...
August 2018: Cellular and Molecular Bioengineering
Jada M Selma, Anusuya Das, Anthony O Awojoodu, Tiffany Wang, Anjan P Kaushik, Quanjun Cui, Hannah Song, Molly E Ogle, Claire E Olingy, Emily G Pendleton, Kayvan F Tehrani, Luke J Mortensen, Edward A Botchwey
Introduction: Mesenchymal stem and progenitor cells (MSCs), which normally reside in the bone marrow, are critical to bone health and can be recruited to sites of traumatic bone injury, contributing to new bone formation. The ability to control the trafficking of MSCs provides therapeutic potential for improving traumatic bone healing and therapy for genetic bone diseases such as hypophosphatasia. Methods: In this study, we explored the sphingosine-1-phosphate (S1P) signaling axis as a means to control the mobilization of MSCs into blood and possibly to recruit MSCs enhancing bone growth...
August 2018: Cellular and Molecular Bioengineering
Settimio Pacelli, Sayantani Basu, Cory Berkland, Jinxi Wang, Arghya Paul
Introduction: Physical and mechanical properties of ceramic-based scaffolds can be modulated by introducing hydrogel coatings on their surface. For instance, hydrogels can be used as elastic layers to overcome the brittleness of synthetic ceramic materials or to control the delivery of essential osteogenic factors. In this work, we aimed to achieve both goals by fabricating a novel cytocompatible hydrogel made of gelatin-alginate as a coating for beta-tricalcium phosphate (β-TCP) scaffolds...
June 2018: Cellular and Molecular Bioengineering
Kenneth A Barbee, Jaimit B Parikh, Yien Liu, Donald G Buerk, Dov Jaron
Introduction: Colocalization of endothelial nitric oxide synthase (eNOS) and capacitative Ca2+ entry (CCE) channels in microdomains such as cavaeolae in endothelial cells (ECs) has been shown to significantly affect intracellular Ca2+ dynamics and NO production, but the effect has not been well quantified. Methods: We developed a two-dimensional continuum model of an EC integrating shear stress-mediated ATP production, intracellular Ca2+ mobilization, and eNOS activation to investigate the effects of spatial colocalization of plasma membrane eNOS and CCE channels on Ca2+ dynamics and NO production in response to flow-induced shear stress...
April 2018: Cellular and Molecular Bioengineering
Nicholas R Anderson, Dooyoung Lee, Daniel A Hammer
Introduction: The leukocyte adhesion cascade is important for the maintenance of homeostasis and the ability of immune cells to access sites of infection and inflammation. Despite much work identifying the molecular components of the cascade, and numerous simulations to predict the relationship between molecule density, identity, and adhesion, these relationships have not been measured experimentally. Methods: Using surfaces functionalized with recombinant ICAM-1 and/or E-selectin along with immobilized SDF-1α, we used a flow chamber to measure rates of tethering, rolling and arrest of primary naïve human CD4+ T lymphocytes on different surface densities of ligand...
April 2018: Cellular and Molecular Bioengineering
Rafael D González-Cruz, Jessica S Sadick, Vera C Fonseca, Eric M Darling
INTRODUCTION: Lamin proteins confer nuclear integrity and relay external mechanical cues that drive changes in gene expression. However, the influence these lamins have on whole-cell mechanical properties is unknown. We hypothesized that protein expression of lamins A, B1, and C would depend on the integrity of the actin cytoskeleton and correlate with cellular elasticity and viscoelasticity. METHODS: To test these hypotheses, we examined the protein expression of lamins A, B1, and C across five different cell lines with varied mechanical properties...
April 2018: Cellular and Molecular Bioengineering
BanuPriya Sridharan, Amy D Laflin, Michael S Detamore
INTRODUCTION: Spheroids of mesenchymal stem cells (MSCs) in cartilage tissue engineering have been shown to enhance regenerative potential owing to their 3D structure. In this study, we explored the possibility of priming spheroids under different media to replace the use of inductive surface coatings for chondrogenic differentiation. METHODS: Rat bone marrow-derived MSCs were organized into cell spheroids by the hanging drop technique and subsequently cultured on hyaluronic acid (HA) coated or non-coated well plates under different cell media conditions...
April 2018: Cellular and Molecular Bioengineering
Emily Tubman, Yungui He, Thomas S Hays, David J Odde
Introduction: The microtubule motor protein kinesin-5 is well known to establish the bipolar spindle by outward sliding of antiparallel interpolar microtubules. In yeast, kinesin-5 also facilitates chromosome alignment "congression" at the spindle equator by preferentially depolymerizing long kinetochore microtubules (kMTs). The motor protein kinesin-8 has also been linked to chromosome congression. Therefore, we sought to determine whether kinesin-5 or kinesin-8 facilitates chromosome congression in insect spindles...
February 2018: Cellular and Molecular Bioengineering
Aniqua Rahman-Zaman, Shuo Shan, Cynthia A Reinhart-King
Introduction: In vivo , cancer cells can utilize tube-like microtracks formed within the extracellular matrix (ECM) of the stroma as 'highways' to escape the primary tumor, however very little is known about the molecular mechanisms that govern cell migration through these microtracks. Cell polarization and actin organization are both essential for efficient cell migration and cells are known to migrate very unidirectionally in confined spaces. In this study, we focused on understanding the role of Girdin during unidirectional migration...
February 2018: Cellular and Molecular Bioengineering
Allison M Claas, Lyla Atta, Simon Gordonov, Aaron S Meyer, Douglas A Lauffenburger
Introduction: Targeted cancer therapeutics have demonstrated more limited clinical efficacy than anticipated, due to both intrinsic and acquired drug resistance. Underlying mechanisms have been largely attributed to genetic changes, but a substantial proportion of resistance observations remain unexplained by genomic properties. Emerging evidence shows that receptor tyrosine kinase (RTK) reprogramming is a major alternative process causing targeted drug resistance, separate from genetic alterations...
2018: Cellular and Molecular Bioengineering
Bradley A Herbig, Scott L Diamond
Introduction: In regions of flow separation/reattachment within diseased arteries, the local hemodynamics can result in stagnation point flow that provides an atypical environment in atherosclerosis. Impinging flows occur with recirculation eddies distal of coronary stenosis or diseased carotid bifurcations. Methods: By perfusing whole blood directly perpendicular to a fibrillar collagen thrombotic surface, a microfluidic device produced a stagnation point flow...
December 2017: Cellular and Molecular Bioengineering
Joseph M Cicchese, Elsje Pienaar, Denise E Kirschner, Jennifer J Linderman
Introduction: Tuberculosis (TB), one of the most common infectious diseases, requires treatment with multiple antibiotics taken over at least 6 months. This long treatment often results in poor patient-adherence, which can lead to the emergence of multi-drug resistant TB. New antibiotic treatment strategies are sorely needed. New antibiotics are being developed or repurposed to treat TB, but as there are numerous potential antibiotics, dosing sizes and potential schedules, the regimen design space for new treatments is too large to search exhaustively...
December 2017: Cellular and Molecular Bioengineering
Yingfei Xue, Cynthia St Hilaire, Luis Hortells, Julie A Phillippi, Vinayak Sant, Shilpa Sant
Introduction: Lack of effective pharmacological treatment makes valvular calcification a significant clinical problem in patients with valvular disease and bioprosthetic/mechanical valve replacement therapies. Elevated levels of reactive oxygen species (ROS) in valve tissue have been identified as a prominent hallmark and driving factor for valvular calcification. However, the therapeutic value of ROS-modulating agents for valvular calcification remains elusive. We hypothesized that ROS-modulating shape-specific cerium oxide nanoparticles (CNPs) will inhibit oxidative stress-induced valvular calcification...
October 2017: Cellular and Molecular Bioengineering
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