Functions of the human papillomavirus type 16 E4 protein

1. Abstract Cervical cancer is thought to be the consequence of infection by human papillomaviruses (HPV). In the majority of cases, DNA from HPV type 16 (HPV16) is found in malignant cervical lesions. The initial steps leading to transformation of an infected cell are not clearly understood but in most cases, disruption and integration of the episomal viral DNA must take place. As a consequence, the E2 and E4 genes are usually not expressed whereas the E6 and E7 oncogenes are highly expressed. However, in a normal infection in which the viral DNA is maintained as an episome, all viral genes are expressed. The pattern according to which the viral proteins are made, and therefore the life cycle of the virus, is tightly linked to the differentiation process of the host keratinocyte. The study of the viral oncogenes E6 and E7 has revealed crucial functions in the process of malignant transformation such as degradation of the p53 tumor suppressor protein, deregulation of the Retinoblastoma protein pathway and activation of the telomerase ribonucleoprotein. All these steps are necessary for cancerous lesions to develop. However, the loss of the E2 gene product seems to be necessary for sufficient expression of E6 and E7 in order to achieve such effects. In normal infections, the E4 protein is made abundantly in the later stages of the viral life cycle. Though extensive amounts of work have been carried out to define the function of E4, it still remains unclear. In this study, several approaches have been used to try and determine the functions of E4. First, a cell-penetrating fusion protein was designed and produced in order to circumvent the chronic difficulties of expressing E4 in mammalian cells. Unfortunately, this approach was not successful due to precipitation of the purified fusion protein. Second, the observation that E4 accumulates in cells having modified their adhesion properties led to the hypothesis that E4 might be involved in the differentiation process of keratinocytes. Preliminary results suggest that E4 triggers differentiation. Last, as E4 has been reported to collapse the cytokeratin network of keratinocytes, a direct approach using atomic force microscopy has allowed us to test the potential modification of mechanical properties of cells harboring reorganized cytokeratin networks. If so, a potential role for E4 in viral particle release could be hypothesized. 2. Résumé Il a été établi que le cancer du col de l'utérus se développe essentiellement à la suite d'une infection par le virus du papillome humain (HPV). Dans la majorité des cas analysés, de l'ADN du HPV de type 16 (HPV16) est détecté. Les étapes initiales de la transformation d'une cellule infectée sont mal connues mais il semble qu'une rupture du génome viral, normalement épisomal, suivi d'une intégration dans le génome de la cellule hôte soient des étapes nécessaires dans la plupart des cas. Or il semble qu'il y ait une sélection pour les cas où l'expression des oncogènes viraux E6 et E7 soit favorisée alors que l'expression des gènes E2 et E4 est en général impossible. Par contre, dans une infection dite normale où le génome viral n'est pas rompu, il n'y pas développement de cancer et tous les gènes viraux sont exprimés. L'ordre dans lequel les protéines virales sont produites, et donc le cycle de réplication du virus, est intimement lié au processus de différentiation de la cellule hôte. L'étude des protéines oncogènes E6 et E7 a révélé des fonctions clés dans le processus de transformation des cellules infectées telles que la dégradation du suppresseur de tumeur p53, la dérégulation de la voie de signalisation Rb ainsi que l'activation de la télomérase. Toutes ces activités sont nécessaires au développement de lésions cancéreuses. Toutefois, il semble que l'expression du gène E2 doit être empêchée afin que suffisamment des protéines E6 et E7 soient produites. Lorsque le gène E2 est exprimé, et donc lorsque le génome viral n'est pas rompu, les protéines E6 et E7 n'entraînent pas de telles conséquences. Le gène E4, qui se trouve dans la séquence codante de E2, a aussi besoin d'un génome viral intact pour être exprimé. Dans une infection normale, le gène E4 est exprimé abondamment dans les dernières étapes de la réplication du virus. Bien que de nombreuses études aient été menées afin de déterminer la fonction virale à E4, aucun résultat n'apparaît évident. Dans ce travail, plusieurs approches ont été utilisées afin d'adresser cette question. Premièrement, une protéine de fusion TAT-E4 a été produite et purifiée. Cette protéine, pouvant entrer dans les cellules vivantes par diffusion au travers de la membrane plasmique, aurait permis d'éviter ainsi les problèmes chroniques rencontrés lors de l'expression de E4 dans les cellules mammifères. Malheureusement, cette stratégie n'a pas pu être utilisée à cause de la précipitation de la protéine purifiée. Ensuite, l'observation que E4 s'accumule dans les cellules ayant modifié leurs propriétés d'adhésion a suggéré que E4 pourrait être impliqué dans le procédé de différentiation des kératinocytes. Des résultats préliminaires supportent cette possibilité. Enfin, il a été montré que E4 pouvait induire une réorganisation du réseau des cytokératines. Une approche directe utilisant le microscope à force atomique nous a ainsi permis de tester une potentielle modification des propriétés mécaniques de cellules ayant modifié leur réseau de cytokératines en présence de E4. Si tel est le cas, un rôle dans la libération de particules virales peut être proposé pour E4.

A Feedfordward Adaptive Controller to Reduce the Imaging Time of Large-Sized Biological Samples with a SPM-Based Multiprobe Station

The time required to image large samples is an important limiting factor in SPM-based systems. In multiprobe setups, especially when working with biological samples, this drawback can make impossible to conduct certain experiments. In this work, we present a feedfordward controller based on bang-bang and adaptive controls. The controls are based in the difference between the maximum speeds that can be used for imaging depending on the flatness of the sample zone. Topographic images of Escherichia coli bacteria samples were acquired using the implemented controllers. Results show that to go faster in the flat zones, rather than using a constant scanning speed for the whole image, speeds up the imaging process of large samples by up to a 4x factor.

Dynamic electrostatic force microscopy in liquid media

We present the implementation of dynamic electrostatic force microscopy in liquid media. This implementation enables the quantitative imaging of local dielectric properties of materials in electrolyte solutions with nanoscale spatial resolution. Local imaging capabilities are obtained by probing the frequency-dependent and ionic concentration-dependent electrostatic forces at high frequency (>1 MHz), while quantification of the interaction forces is obtained with finite-element numerical calculations. The results presented open a wide range of possibilities in a number of fields where the dielectric properties of materials need to be probed at the nanoscale and in a liquid environment.

Dynamic electrostatic force microscopy in liquid media

We present the implementation of dynamic electrostatic force microscopy in liquid media. This implementation enables the quantitative imaging of local dielectric properties of materials in electrolyte solutions with nanoscale spatial resolution. Local imaging capabilities are obtained by probing the frequency-dependent and ionic concentration-dependent electrostatic forces at high frequency (>1 MHz), while quantification of the interaction forces is obtained with finite-element numerical calculations. The results presented open a wide range of possibilities in a number of fields where the dielectric properties of materials need to be probed at the nanoscale and in a liquid environment.

Surface characterization of chemically modified fiber, wood and paper

Inorganic-organic sol-gel hybrid coatings can be used for improving and modifying properties of wood-based materials. By selecting a proper precursor, wood can be made water repellent, decay-, moisture- or UV-resistant. However, to control the barrier properties of sol-gel coatings on wood substrates against moisture uptake and weathering, an understanding of the surface morphology and chemistry of the deposited sol-gel coatings on wood substrates is needed. Mechanical pulp is used in production of wood-containing printing papers. The physical and chemical fiber surface characteristics, as created in the chosen mechanical pulp manufacturing process, play a key role in controlling the properties of the end-use product. A detailed understanding of how process parameters influence fiber surfaces can help improving cost-effectiveness of pulp and paper production. The current work focuses on physico-chemical characterization of modified wood-based materials with surface sensitive analytical tools. The overall objectives were, through advanced microscopy and chemical analysis techniques, (i) to collect versatile information about the surface structures of Norway spruce thermomechanical pulp fiber walls and understand how they are influenced by the selected chemical treatments, and (ii) to clarify the effect of various sol-gel coatings on surface structural and chemical properties of wood-based substrates. A special emphasis was on understanding the effect of sol-gel coatings on the water repellency of modified wood and paper surfaces. In the first part of the work, effects of chemical treatment on micro- and nano-scale surface structure of 1st stage TMP latewood fibers from Norway spruce were investigated. The chemicals applied were buffered sodium oxalate and hydrochloric acid. The outer and the inner fiber wall layers of the untreated and chemically treated fibers were separately analyzed by light microscopy, atomic force microscopy and field-emission scanning electron microscopy. The selected characterization methods enabled the demonstration of the effect of different treatments on the fiber surface structure, both visually and quantitatively. The outer fiber wall areas appeared as intact bands surrounding the fiber and they were clearly rougher than areas of exposed inner fiber wall. The roughness of the outer fiber wall areas increased most in the sodium oxalate treatment. The results indicated formation of more surface pores on the exposed inner fiber wall areas than on the corresponding outer fiber wall areas as a result of the chemical treatments. The hydrochloric acid treatment seemed to increase the surface porosity of the inner wall areas. In the second part of the work, three silane-based sol-gel hybrid coatings were selected in order to improve moisture resistance of wood and paper substrates. The coatings differed from each other in terms of having different alkyl (CH3–, CH3-(CH2)7–) and fluorocarbon (CF3–) chains attached to the trialkoxysilane sol-gel precursor. The sol-gel coatings were deposited by a wet coating method, i.e. spraying or spreading by brush. The effect of solgel coatings on surface structural and chemical properties of wood-based substrates was studied by using advanced surface analyzing tools: atomic force microscopy, X-ray photoelectron spectroscopy and time-of-flight secondary ion spectroscopy. The results show that the applied sol-gel coatings, deposited as thin films or particulate coatings, have different effects on surface characteristics of wood and wood-based materials. The coating which has a long hydrocarbon chain (CH3-(CH2)7–) attached to the silane backbone (octyltriethoxysilane) produced the highest hydrophobicity for wood and wood-based materials.

Bioimage informatics in STED super-resolution microscopy

Optical microscopy is living its renaissance. The diffraction limit, although still physically true, plays a minor role in the achievable resolution in far-field fluorescence microscopy. Super-resolution techniques enable fluorescence microscopy at nearly molecular resolution. Modern (super-resolution) microscopy methods rely strongly on software. Software tools are needed all the way from data acquisition, data storage, image reconstruction, restoration and alignment, to quantitative image analysis and image visualization. These tools play a key role in all aspects of microscopy today – and their importance in the coming years is certainly going to increase, when microscopy little-by-little transitions from single cells into more complex and even living model systems. In this thesis, a series of bioimage informatics software tools are introduced for STED super-resolution microscopy. Tomographic reconstruction software, coupled with a novel image acquisition method STED< is shown to enable axial (3D) super-resolution imaging in a standard 2D-STED microscope. Software tools are introduced for STED super-resolution correlative imaging with transmission electron microscopes or atomic force microscopes. A novel method for automatically ranking image quality within microscope image datasets is introduced, and it is utilized to for example select the best images in a STED microscope image dataset.

Supramolecular polymers azo-containing : photo-responsive block copolymer elastomers and homopolymers

Beaucoup d'efforts dans le domaine des matériaux polymères sont déployés pour développer de nouveaux matériaux fonctionnels pour des applications spécifiques, souvent très sophistiquées, en employant des méthodes simplifiées de synthèse et de préparation. Cette thèse porte sur les polymères photosensibles – i.e. des matériaux fonctionnels qui répondent de diverses manières à la lumière – qui sont préparés à l'aide de la chimie supramoléculaire – i.e. une méthode de préparation qui repose sur l'auto-assemblage spontané de motifs moléculaires plus simples via des interactions non covalentes pour former le matériau final désiré. Deux types de matériaux photosensibles ont été ciblés, à savoir les élastomères thermoplastiques à base de copolymères à blocs (TPE) et les complexes d'homopolymères photosensibles. Les TPEs sont des matériaux bien connus, et même commercialisés, qui sont généralement composés d’un copolymère tribloc, avec un bloc central très flexible et des blocs terminaux rigides qui présentent une séparation de phase menant à des domaines durs isolés, composés des blocs terminaux rigides, dans une matrice molle formée du bloc central flexible, et ils ont l'avantage d'être recyclable. Pour la première fois, au meilleur de notre connaissance, nous avons préparé ces matériaux avec des propriétés photosensibles, basé sur la complexation supramoléculaire entre un copolymère tribloc simple parent et une petite molécule possédant une fonctionnalité photosensible via un groupe azobenzène. Plus précisément, il s’agit de la complexation ionique entre la forme quaternisée d'un copolymère à blocs, le poly(méthacrylate de diméthylaminoéthyle)-poly(acrylate de n-butyle)-poly(méthacrylate de diméthylaminoéthyle) (PDM-PnBA-PDM), synthétisé par polymérisation radicalaire par transfert d’atomes (ATRP), et l'orange de méthyle (MO), un composé azo disponible commercialement comportant un groupement SO3 -. Le PnBA possède une température de transition vitreuse en dessous de la température ambiante (-46 °C) et les blocs terminaux de PDM complexés avec le MO ont une température de transition vitreuse élevée (140-180 °C, en fonction de la masse molaire). Des tests simples d'élasticité montrent que les copolymères à blocs complexés avec des fractions massiques allant de 20 à 30% présentent un caractère élastomère. Des mesures d’AFM et de TEM (microscopie à force atomique et électronique à ii transmission) de films préparés à l’aide de la méthode de la tournette, montrent une corrélation entre le caractère élastomère et les morphologies où les blocs rigides forment une phase minoritaire dispersée (domaines sphériques ou cylindriques courts). Une phase dure continue (morphologie inversée) est observée pour une fraction massique en blocs rigides d'environ 37%, ce qui est beaucoup plus faible que celle observée pour les copolymères à blocs neutres, dû aux interactions ioniques. La réversibilité de la photoisomérisation a été démontrée pour ces matériaux, à la fois en solution et sous forme de film. La synthèse du copolymère à blocs PDM-PnBA-PDM a ensuite été optimisée en utilisant la technique d'échange d'halogène en ATRP, ainsi qu’en apportant d'autres modifications à la recette de polymérisation. Des produits monodisperses ont été obtenus à la fois pour la macroamorceur et le copolymère à blocs. À partir d'un seul copolymère à blocs parent, une série de copolymères à blocs partiellement/complètement quaternisés et complexés ont été préparés. Des tests préliminaires de traction sur les copolymères à blocs complexés avec le MO ont montré que leur élasticité est corrélée avec la fraction massique du bloc dur, qui peut être ajustée par le degré de quaternisation et de complexation. Finalement, une série de complexes d'homopolymères auto-assemblés à partir du PDM et de trois dérivés azobenzènes portant des groupes (OH, COOH et SO3) capables d'interactions directionnelles avec le groupement amino du PDM ont été préparés, où les dérivés azo sont associés avec le PDM, respectivement, via des interactions hydrogène, des liaisons ioniques combinées à une liaison hydrogène à travers un transfert de proton (acidebase), et des interactions purement ioniques. L'influence de la teneur en azo et du type de liaison sur la facilité d’inscription des réseaux de diffraction (SRG) a été étudiée. L’efficacité de diffraction des SRGs et la profondeur des réseaux inscrits à partir de films préparés à la méthode de la tournette montrent que la liaison ionique et une teneur élevée en azo conduit à une formation plus efficace des SRGs.

Production of carbon nanotubes by PECVD and their applications to supercapacitors

Màster en Nanociència i Nanotecnologia

Swift heavy ion induced surface and microstructural evolution in metallic glass thin films

Swift heavy ion induced changes in microstructure and surface morphology of vapor deposited Fe–Ni based metallic glass thin films have been investigated by using atomic force microscopy, X-ray diffraction and transmission electron microscopy. Ion beam irradiation was carried out at room temperature with 103 MeV Au9+ beam with fluences ranging from 3 1011 to 3 1013 ions/cm2. The atomic force microscopy images were subjected to power spectral density analysis and roughness analysis using an image analysis software. Clusters were found in the image of as-deposited samples, which indicates that the film growth is dominated by the island growth mode. As-deposited films were amorphous as evidenced from X-ray diffraction; however, high resolution transmission electron microscopy measurements revealed a short range atomic order in the samples with crystallites of size around 3 nm embedded in an amorphous matrix. X-ray diffraction pattern of the as-deposited films after irradiation does not show any appreciable changes, indicating that the passage of swift heavy ions stabilizes the short range atomic ordering, or even creates further amorphization. The crystallinity of the as-deposited Fe–Ni based films was improved by thermal annealing, and diffraction results indicated that ion beam irradiation on annealed samples results in grain fragmentation. On bombarding annealed films, the surface roughness of the films decreased initially, then, at higher fluences it increased. The observed change in surface morphology of the irradiated films is attributed to the interplay between ion induced sputtering, volume diffusion and surface diffusion

Silbernanoteilchen auf Magnesiumoxid - Über den Vergleich von optischer Spektroskopie, Rasterkraftmikroskopie und Transmissionselektronenmikroskopie

In der vorliegenden Arbeit wurde das Wachstum von Silbernanoteilchen auf Magnesiumoxid und dabei insbesondere deren Größen- und Formrelation untersucht. Hierzu wurden Silbernanoteilchen auf ausgedehnten Magnesiumoxidsubstraten sowie auf Magnesiumoxid-Nanowürfeln präpariert. Zur Charakterisierung wurde die optische Spektroskopie, die Rasterkraftmikroskopie und die Transmissionselektronenmikroskopie eingesetzt. Während die Elektronenmikroskopie direkt sehr exakte Daten bezüglich der Größe und Form der Nanoteilchen liefert, kann mit den beiden anderen in dieser Arbeit verwendeten Charakterisierungsmethoden jeweils nur ein Parameter bestimmt werden. So kann man die Größe der Nanoteilchen indirekt mit Hilfe des AFM, durch Messung der Teilchananzahldichte, bestimmen. Bei der Bestimmung der Form mittels optischer Spektroskopie nutzt man aus, dass die spektralen Positionen der Plasmonresonanzen in dem hier verwendeten Größenbereich von etwa 2 - 10~nm nur von der Form aber nicht von der Größe der Teilchen abhängen. Ein wesentliches Ziel dieser Arbeit war es, die Ergebnisse bezüglich der Form und Größe der Nanoteilchen, die mit den unterschiedlichen Messmethoden erhalten worden sind zu vergleichen. Dabei hat sich gezeigt, dass die mit dem AFM und dem TEM bestimmten Größen signifikant voneinander Abweichen. Zur Aufklärung dieser Diskrepanz wurde ein geometrisches Modell aufgestellt und AFM-Bilder von Nanoteilchen simuliert. Bei dem Vergleich von optischer Spektroskopie und Transmissionselektronenmikroskopie wurde eine recht gute Übereinstimmung zwischen den ermittelten Teilchenformen gefunden. Hierfür wurden die gemessenen optischen Spektren mit Modellrechnungen verglichen, woraus man die Relation zwischen Teilchengröße und -form erhielt. Eine Übereinstimmung zwischen den erhaltenen Daten ergibt sich nur, wenn bei der Modellierung der Spektren die Form- und Größenverteilung der Nanoteilchen berücksichtigt wird. Insgesamt hat diese Arbeit gezeigt, dass die Kombination von Rasterkraftmikroskopie und optischer Spektroskopie ein vielseitiges Charakterisierungsverfahren für Nanoteilchen. Die daraus gewonnenen Ergebnisse sind innerhalb gewisser Fehlergrenzen gut mit der Transmissionselektronenmikroskopie vergleichbar.

A Morphological View of the Sodium 4,4 `-Distyrylbiphenyl Sulfonate Fluorescent Brightness Distribution on Regenerated Cellulose Fibers

Evidence of the sorption of the whitening agent sodium 4,4`-distyrylbiphenyl sulfonate in the presence of the anionic surfactant sodium dodecylsulfate or the cationic surfactant dodecyl trimethyl ammonium chloride on regenerated cellulose fibers is given by several microscopy techniques. Scanning electron microscopy provided images of the cylindrical fibers with dimensions of 3.5 cm (length) and 13.3 mu m (thickness), with empty cores of 1 mu m diameter and a smooth surface. Atomic force microscopy showed a fiber surface with disoriented nanometric domains using both tapping-mode height and phase image modes. Atomic force microscopy also showed that the whitening agent and surfactant molecules were sorbed onto the fiber surface, in agreement with the adsolubilization sorption model. Transmission electron microscopy showed fibers with nanometric parallel cylinders, surrounded by holes where the fluorescent whitening molecules accumulated. On the basis of these techniques, we conclude that the sorption process occurs preferentially on the fiber surface in contact with the water solution, and under saturated conditions, the whitening agent penetrates into the pores and are simultaneously sorbed on the pore walls bulk, forming molecular aggregates. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 2321-2327, 2010

Platinum nanoparticle-modified electrodes, morphologic, and electrochemical studies concerning electroactive materials deposition

The present work describes the synthesis of platinum nanoparticles followed by their electrophoretic deposition onto transparent fluorine-doped tin oxide electrodes. The nano-Pt-modified electrodes were characterized by voltammetric studies in acidic solutions showing a great electrocatalytic behavior towards H(+) reduction being very interesting for fuel cell applications. Morphological characterization was performed by atomic force microscopy on different modified electrodes showing a very rough surface which can be tuned by means of time of deposition. Also, nickel hydroxide thin films were galvanostatically grown onto these electrodes showing an interesting electrochemical behavior as sharper peaks, indicating a faster ionic exchange from the electrolyte to the film.

Influência das espécies do plasma de N2 + O2 nas propriedades físicoquímicas das superfícies do pet

This work reports the influence of the poly (ethylene terephthalate) textile and films surface modification by plasmas of O2 and mixtures (N2 + O2), on their physical and chemical properties. The plasma surface polymeric modification has been used for many researchs, because it does not affect the environment with toxic agents, the alterations remains only at nanometric layers and this technique shows expressive results. Then, due to its good acceptance, the treatment was carried out in a vacuum chamber. Some parameters remained constant during all treatment, such as: Voltage 470 V; Pressure 1,250 Mbar; Current: 0, 10 A and gas flow: 10 cm3/min, using oxygen plasma alternating the treatment time 10 to 60 min with an increase of 10 min to each subsequent treatment. Also, the samples were treated with a gas mixture (nitrogen + oxygen) which was varied only the gas composition from 0 to 100% leaving the treatment time remaining constant to all treatment (10 min). The plasma treatment was characterized in-situ with Optics Emission Spectroscopy (OES), and the samples was characterized by contact angle, surface tension, Through Capillary tests, Raman spectroscopy, Infrared attenuated total reflection (IR-ATR) and atomic force microscopy, scanning electronic Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS). The results showed that oxygen treated fabrics presented high wettability, due to the hydrophilic groups incorporation onto the surface formed through spputering of carbon atoms. For the nitrogen atmosphere, there is the a film deposition of amine groups. Treatment with small oxygen concentration in the mixture with nitrogen has a higher spputered species of the samples

Modificação superficial de filmes de poliéster usando plasma a baixa temperatura

A polyester film has a vast application field, due some properties that are inherent of this kind of material such as, good mechanical resistance, chemical resistance to acids and bases and low production cost. However, this material has some limitations as low superficial tension, flat surface, low affinity to dyers, and poor adhesion which impede the use of the same ones for some finality as good wettability. Among the existent techniques to increase the superficial tension, plasma as energy source is the more promising technique, because of their versatility and for not polluting the environment. The plasma surface polymeric modification has been used for many researchers, because it does not affect the environment with toxic agents, the alterations remains only at nanometric layers and this technique shows expressive results. Then, due to its good acceptance, polyester films were treated with oxygen plasma varying the treatment time from 10 to 60 min with an increase of 10 min to each subsequent treatment. Also, the samples were treated with a gas mixture (nitrogen + oxygen) varying the percentage of each gas the mixture from 0 to 100%, the treatment time remaining constant to all treatments (10 min). After plasma treatment the samples were characterized by contact angle, surface tension, Raman spectroscopy, Infrared attenuated total reflection (IR-ATR) and atomic force microscopy, with the aim to study the wettability increase of treated polyester films as its variables. In the (O2/N2) plasma treatment of polyester films can be observed an increase of superficial roughness superior to those treated by O2 plasma. By the other hand, the chemical modification through the implantation of polar groups at the surface is obtained more easily using O2 plasma treatment

Isolation of nanocellulose from pineapple leaf fibres by steam explosion

Steam explosion process is employed for the successful extraction of cellulose nanofibrils from pineapple leaf fibres for the first time. Steam coupled acid treatment on the pineapple leaf fibres is found to be effective in the depolymerization and defibrillation of the fibre to produce nanofibrils of these fibres. The chemical constituents of the different stages of pineapple fibres undergoing treatment were analyzed according to the ASTM standards. The crystallinity of the fibres is examined from the XRD analysis. Characterization of the fibres by SEM. AFM and TEM supports the evidence for the successful isolation of nanofibrils from pineapple leaf. The developed nanocellulose promises to be a very versatile material having the wide range of biomedical applications and biotechnological applications, such as tissue engineering, drug delivery, wound dressings and medical implants. (C) 2010 Elsevier Ltd. All rights reserved.