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Full-Text Articles in Cell Biology

Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov Nov 2014

Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov

GSBS Dissertations and Theses

Over 600,000 bone-grafting operations are performed each year in the United States. The majority of the bone used for these surgeries comes from autografts that are limited in quantity or allografts with high failure rates. Current synthetic bone grafting materials have poor mechanical properties, handling characteristics, and bioactivity. The goal of this dissertation was to develop a clinically translatable bone tissue engineering scaffold with improved handling characteristics, bioactivity, and smart delivery modalities. We hypothesized that this could be achieved through the rational selection of Food and Drug Administration (FDA) approved materials that blend favorably with hydroxyapatite (HA), the principle ...


Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson Oct 2014

Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson

Open Access Dissertations

The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of ...


Impedance Biosensors For The Rapid Detection Of Viral And Bacterial Pathogens Using Avian Influenza Virus Subtypes H5n1 And H7n2 And Escherichia Coli O157:H7 As Model Targets, Jacob David Lum Aug 2014

Impedance Biosensors For The Rapid Detection Of Viral And Bacterial Pathogens Using Avian Influenza Virus Subtypes H5n1 And H7n2 And Escherichia Coli O157:H7 As Model Targets, Jacob David Lum

Theses and Dissertations

This research investigated impedance biosensors for the rapid detection of viral and bacterial pathogens using avian influenza virus (AIV) subtypes H5N1 and H7N2 and Escherichia coli O157:H7 as the model targets, which were chosen due to their impact on the agricultural and food industries. For the detection of AIV H7N2, a single stranded DNA aptamer was selected using systematic evolution of ligands by exponential enrichment (SELEX). The selected aptamer and a previously selected aptamer against AIV H5N1 were used in a microfluidics chip with an embedded interdigitated array microelectrode to fabricate an impedance biosensor for specific detection of AIV ...


Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang Aug 2014

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important ...


Cellular Contractility And Extracellular Matrix Stiffness Regulate Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Haage, Ian C. Schneider Aug 2014

Cellular Contractility And Extracellular Matrix Stiffness Regulate Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Haage, Ian C. Schneider

Chemical and Biological Engineering Publications

The pathogenesis of cancer is often driven by local invasion and metastasis. Recently, mechanical properties of the tumor microenvironment have been identified as potent regulators of invasion and metastasis, while matrix metalloproteinases (MMPs) are classically known as significant enhancers of cancer cell migration and invasion. Here we have been able to sensitively measure MMP activity changes in response to specific extracellular matrix (ECM) environments and cell contractility states. A pancreatic cancer cell line, Panc-1 cells, up-regulate MMP activities between 3- and 10- fold with increased cell contractility. Conversely, they down-regulate MMP activities when contractility is blocked to levels seen with ...


High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song May 2014

High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song

UMass Center for Clinical and Translational Science Research Retreat

There is a critical clinical need for alternatives to autograft and allograft bone for over 500,000 bone grafting operations performed each year in the United States. Current synthetic bone grafts suffer from poor handling characteristics, brittle mechanical properties, and inconsistent bioactivity. By blending a biodegradable amphiphilic polymer with hydroxyapatite (HA), the main mineral component in bone, we developed an improved synthetic bone graft. The polymer/HA composites were fabricated in both 2-D and 3-D forms by electrospinning and 3-D printing. These materials exhibited unique handling characteristics such as high tensile elasticity (>200% failure strain) and self-stiffening properties upon hydration ...


Multiple Approaches To Determine Toxicity Of Micro And Nano-Sized Titanium Dioxide Materials When Exposed To Human Red Blood Cells, Aaron Stella, Shu-Feng Hsieh, Dhimiter Bello, Daniel Schmidt, Eugene Rodgers May 2014

Multiple Approaches To Determine Toxicity Of Micro And Nano-Sized Titanium Dioxide Materials When Exposed To Human Red Blood Cells, Aaron Stella, Shu-Feng Hsieh, Dhimiter Bello, Daniel Schmidt, Eugene Rodgers

UMass Center for Clinical and Translational Science Research Retreat

Introduction: The utility of engineered nanomaterials’ is growing, particularly the titanium dioxide (TiO2) polymorphs. TiO2 is very useful for brightening paints, and coloring foods. Nano-sized TiO2 is also useful for sunscreens, cosmetics, and can be utilized as a photocatalyst. However, the nanometer size and the large specific surface area of the TiO2 materials are physicochemical characteristics which may contribute to human red blood cell (RBC) damage. Using RBCs as a cellular model, we have evaluated the effects of TiO2 nanoparticle exposure to RBCs by quantifying oxidized glutathione, oxidized membrane vitamin E, hemolysis, hemoglobin adsorption, and cellular aggregation. Results: Red blood ...


The Number Of Lines A Cell Contacts And Cell Contractility Drive The Efficiency Of Contact Guidance, Nicholas R. Romsey, Yue Hou, Laura L. Rodriguez, Ian C. Schneider Mar 2014

The Number Of Lines A Cell Contacts And Cell Contractility Drive The Efficiency Of Contact Guidance, Nicholas R. Romsey, Yue Hou, Laura L. Rodriguez, Ian C. Schneider

Chemical and Biological Engineering Publications

Cell migration is an important biological function that impacts many physiological and pathological processes. Often migration is directed along various densities of aligned fibers of collagen, a process called contact guidance. However, cells adhere to other components in the extracellular matrix, possibly affecting migrational behavior. Additionally, changes in intracellular contractility are well known to affect random migration, but its effect on contact guidance is less known. This study examines differences in directed migration in response to variations in the spacing of collagen, non-specific background adhesion strength and myosin II-mediated contractility. Collagen was microcontact printed onto glass substrates and timelapse live-cell ...


Synthesis And Functionalization Of Gold Nanoparticles Using Chemically Modified Ssdna, Philip Gerard Calabrese Jan 2014

Synthesis And Functionalization Of Gold Nanoparticles Using Chemically Modified Ssdna, Philip Gerard Calabrese

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

In the first part of this thesis, methods for functionalizing spherical gold nanoparticles with nucleic acid binding ligands (aptamers) that target the VEGF receptor complex were developed. In order to provide a multiplexed labeling strategy for imaging the VEGF receptor complex in electron microscopy, gold nanoparticles of distinct sizes were conjugated to modified ssDNA aptamers that target the VEGF-A cytokine, the VEGFR-2 RTK receptor and a membrane associated co-receptor, Nrp-1. The modified ssDNA gold nanoparticle conjugates were applied to a human lung carcinoma cell line (A549) which has been shown to express each of these proteins and used as a ...


Collagen Attachment To The Substrate Controls Cell Clustering Through Migration, Yue Hou, Laura L. Rodriguez, Juan Wang, Ian C. Schneider Jan 2014

Collagen Attachment To The Substrate Controls Cell Clustering Through Migration, Yue Hou, Laura L. Rodriguez, Juan Wang, Ian C. Schneider

Chemical and Biological Engineering Publications

Cell clustering and scattering play important roles in cancer progression and tissue engineering. While the extracellular matrix (ECM) is known to control cell clustering, much of the quantitative work has focused on the analysis of clustering between cells with strong cell-cell junctions. Much less is known about how the ECM regulates cells with weak cell-cell contact. Clustering characteristics were quantified in rat adenocarcinoma cells, which form clusters on physically adsorbed collagen substrates, but not on covalently attached collagen substrates. Covalently attaching collagen inhibited desorption of collagen from the surface. While changes in proliferation rate could not explain differences seen in ...


Design And Fabrication Of Engineered Platforms To Control Multiple Cue Directed Cell Migration, Laura M. Lara-Rodriguez Jan 2014

Design And Fabrication Of Engineered Platforms To Control Multiple Cue Directed Cell Migration, Laura M. Lara-Rodriguez

Graduate Theses and Dissertations

Cell migration is essential during a variety of physiological events, and as such it has been extensively studied in an attempt to unravel the details of its mechanisms. Cells receive information from the environment and migrate accordingly. Within the last few decades, different studies have evaluated the effect of different types of signals and the way in which they regulate cell migration. However, cells do not respond to individual cues, but they are constantly receiving information from a variety of signals in vivo. One particular scenario in which the concerted action of multiple signals is thought to be relevant is ...


Regulation Of Cell Signaling By Mig6 And Sprouty2 In Cancers With Egfr Mutations, Alice Macdonald Walsh Jan 2014

Regulation Of Cell Signaling By Mig6 And Sprouty2 In Cancers With Egfr Mutations, Alice Macdonald Walsh

Publicly Accessible Penn Dissertations

Epidermal growth factor receptor (EGFR) mutation and overexpression promote tumorigenesis in multiple cancers. Understanding the complex EGFR regulatory network is critical for developing effective therapeutic interventions. To this end, this work investigated the functions of two incompletely characterized regulators of EGFR trafficking and signaling, mitogen-inducible gene 6 (MIG6) and Sprouty2 (SPRY2), in two cancer settings where EGFR mutation is common, non-small cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). In NSCLC cells, results indicate that MIG6, an endogenous inhibitor of EGFR activity and endocytic adaptor, is surprisingly responsible for at least half of EGFR endocytosis, suggesting that a substantial fraction ...


Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal Jan 2014

Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal

Publicly Accessible Penn Dissertations

Whether a stem cell remains or egresses away from its physiological niche is a function of mechanical and soluble factors in a time-dependent manner, which implicates a `memory' of prior mechanochemical conditioning. Virtually every organ in the body contains resident stem or progenitor cells that contribute to organ homeostasis or repair. The wound healing process in higher vertebrate animals is spatiotemporally complex and usually leads to scarring. Limitations for the use of stem cells as regenerative therapy include the lack of expansion capabilities in vitro as well as materials issues that complicate traditional biochemical protocols. A minimal `scar in a ...


Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler Jan 2014

Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler

Publicly Accessible Penn Dissertations

Hematopoiesis in human bone marrow generates every second about 105 – 106 anucleated platelets and red blood cells as well as nucleated white blood cells that are capable of infiltrating distant tissues. The thesis begins in the marrow with a description of (1) nuclear membrane ‘lamina’ physicochemical properties that influence marrow-to-circulation trafficking, and proceeds to detail (2) the physicochemical roles of membrane cortex ‘myosin’ in key marrow processes of motility and division as well as platelet biogenesis and disease. The thesis finishes with (3) studies of macrophages in peripheral tissues far from the marrow and aspects of how such ...


Dielectric Characterization Of Coastal Cartilage Chondrocytes, Michael W. Stacey, Ahmet C. Sabuncu, Ali Beskok Jan 2014

Dielectric Characterization Of Coastal Cartilage Chondrocytes, Michael W. Stacey, Ahmet C. Sabuncu, Ali Beskok

Bioelectrics Publications

BACKGROUND: Chondrocytes respond to biomechanical and bioelectrochemical stimuli by secreting appropriate extracellular matrix proteins that enable the tissue to withstand the large forces it experiences. Although biomechanical aspects of cartilage are well described, little is known of the bioelectrochemical responses. The focus of this study is to identify bioelectrical characteristics of human costal cartilage cells using dielectric spectroscopy.

METHODS: Dielectric spectroscopy allows non-invasive probing of biological cells. An in house computer program is developed to extract dielectric properties of human costal cartilage cells from raw cell suspension impedance data measured by a microfluidic device. The dielectric properties of chondrocytes are ...


Introduction To Fourth Special Issue On Electroporation-Based Technologies And Treatments, Damijan Miklavčič, Lluis M. Mir, P. Thomas Vernier Jan 2014

Introduction To Fourth Special Issue On Electroporation-Based Technologies And Treatments, Damijan Miklavčič, Lluis M. Mir, P. Thomas Vernier

Bioelectrics Publications

This fourth special electroporation-based technologies and treatments issue of the Journal of Membrane Biology contains reports on recent developments in the field of electroporation by participants in the 7th International Workshop and Postgraduate Course on electroporation based technologies and treatments (EBTT 2013) held in Ljubljana, November 17–23, 2013. The 65 participants included faculty members, invited lecturers, special guests, and young scientists, and students from 16 countries. In addition to lectures on the fundamentals, this year’s sessions included talks on microbial inactivation by pulsed electric fields, modeling of intracellular electroporation, electroporation in food processing, and electrotransfer-facilitated DNA vaccination.


Engineered Materials To Measure And Regulate Cell Mechanotransduction, Brandon Lou Blakely Jan 2014

Engineered Materials To Measure And Regulate Cell Mechanotransduction, Brandon Lou Blakely

Publicly Accessible Penn Dissertations

The extracellular environment plays a key role in a wide array of cellular functions including migration, tissue formation, and differentiation. This thesis overviews the design of a molecular sensor to measure cellular forces and a hydrogel system to engineer angiogenic sprouting. We developed molecular force probes (FPs) that report traction forces of adherent cells with high spatial resolution, can be linked to virtually any surface, and do not require monitoring deformations of elastic substrates. FPs consist of DNA hairpins conjugated to fluorophore-quencher pairs that unfold and fluoresce when subjected to specific amounts of force. In chapter two we overview the ...