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Book Modeling of Interactions Between Nanoparticles and Cell Membranes

Download or read book Modeling of Interactions Between Nanoparticles and Cell Membranes written by Young-Min Ban and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The hydrophobic interaction between the particles and membrane core induces the strong coupling between the nanoparticle motion and membrane deformation. It is observed that the considered nanoparticles affect several physical properties of the membrane. The nanoparticles embedded into the membrane interior lead to the membrane softening, which becomes more significant with increase in CNT length and concentration. The lateral pressure profile and membrane energy in the membrane containing the nanoparticles exhibit localized perturbation around the nanoparticle. The nanoparticles are not likely to affect membrane protein function by the weak perturbation of the internal stress in the membrane. Due to the short-ranged interactions between the nanoparticles, the nanoparticles would not form aggregates inside membranes. The effect of lipid peroxidation on cell membrane deformation is assessed. The peroxidized lipids introduce a perturbation to the internal structure of the membrane leading to higher amplitude of the membrane fluctuations. Higher concentration of the peroxidized lipids induces more significant perturbation. Cumulative effects of lipid peroxidation caused by nanoparticles are examined for the first time. The considered amphiphilic particle appears to reduce the perturbation of the membrane structure at its equilibrium position inside the peroxidized membrane. This suggests a possibility of antioxidant effect of the nanoparticle.

Book Characterizing Nanoparticle Interactions at the Cellular Membrane

Download or read book Characterizing Nanoparticle Interactions at the Cellular Membrane written by Arielle Christen Mensch and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: As the use of nanotechnology continues to rise, the release of engineered nanomaterials into the environment becomes inevitable. A need exists to understand the implications of engineered nanomaterials and to develop sustainable alternatives as adverse impacts are uncovered. In order to reduce any negative impacts of nanomaterials and exploit any beneficial impacts, the field of environmental nanotechnology must aim to understand the behavior of nanomaterials in complex environments through the use of [in situ] analytical methods and utilize model systems (both in terms of nanomaterials and organisms) to determine the chemical factors that drive nanoparticle behavior. The work presented here focuses on the cellular membrane, which is hypothesized to be the first point of contact between a nanomaterial and an organism. The characterization of different models cellular membranes and the characterization of nanoparticle interactions at these model membranes are presented. First, we investigated the impact of natural organic matter (NOM), which is found ubiquitously in the environment, on the interactions between polymer wrapped diamond nanoparticles (DNPs) and lipopolysaccharide-containing supported lipid bilayers, a model for Gram-negative bacteria cell membranes. To demonstrate the relevance of our model system we extended our study to include experiments using a Gram-negative bacterium, [Shewanella oneidensis] MR-1. We found that NOM impacted the hydrodynamic and electrokinetic properties of DNPs in a concentration dependent manner, which altered subsequent interactions with both model and actual biological membranes. Our results demonstrate that the effects of NOM coronas on nanoparticle properties and interactions with biological surfaces can depend on the relative amounts of NOM and nanoparticles. We then examined the impact of polymer wrapped quantum dots (QDs) on supported lipid bilayers containing important biomolecules found in the outer membrane of eukaryotic cells (cholesterol and sphingomyelin). We used [in situ] analytical methods to study these interactions in real time and found that the QDs caused structural changes to the bilayers studied. Quartz crystal microbalance with dissipation monitoring coupled with nanoplasmonic sensing revealed favorable interaction between the QDs and the bilayers. Increases in dissipation and apparent mass gains upon rinse suggested structural rearrangement was occurring. Time-lapsed atomic force microscopy confirmed this hypothesis and revealed the disappearance of phase-segregated domains upon interaction with the QDs. Our results demonstrate the importance of using complementary [in situ] analytical methods to understand the complex interactions that occur at the cellular membrane. We next demonstrate the powerful capabilities of atomic force microscopy for imaging and characterizing biological membranes. We investigate the impact of the substrate in the formation and characteristics of phase-segregated domains in supported lipid bilayers. We considered commonly used substrates in different analytical techniques (e.g., mica, silica, and glass). We discussed the importance of considering the substrate in drawing conclusions across different techniques. We also demonstrated the spatial and temporal correlation of atomic force and fluorescence microscopy. Finally, we extended our work using atomic force microscopy and developed a protocol to image and characterize the mechanical properties of fixed and live rainbow trout ([Oncorhynchus mykiss]) gill epithelial cells. We discussed various experimental variables such as instrumental parameters, type of AFM probe used, and the confluency of the cells on the substrate. We found that the ideal imaging conditions included using an AFM probe with a low spring constant and relatively dull tip, working with cells grown to ~75% confluency, and scanning at low speeds, high amplitudes, and minimal forces. We showed that fixed trout gill cells had an increased height and modulus value as compared to live cells. This work demonstrated the first example of AFM imaging and mechanical mapping on either fixed or live trout gill cells and set a protocol to examine the impacts of different stressors, such as nanomaterials, on trout gill cells.

Book Analytical Models to Understand Interactions at the Nano bio Interface

Download or read book Analytical Models to Understand Interactions at the Nano bio Interface written by Christian A. Reardon-Lochbaum and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanomaterials are synthesized for use in a wide variety of consumer and industrial products, which will inadvertently lead to nanomaterial exposure to biological systems; additionally, nanomaterials are being explored for application in both the medical and agricultural fields, which constitutes intentional nanomaterial exposure to biological systems. With the rapid expansion in the quantity and variety of nanomaterials being synthesized, it has become a huge undertaking to characterize the interactions at the nano-bio interface. Here, I present a series of studies that work towards developing and utilizing model systems to characterize interactions between nanomaterials and cellular membranes or biological fluids. This work targets two model membrane systems-the supported lipid bilayer and unilamellar vesicles-and one biological fluid model system-plant xylem fluid. Membranes make up one of the cells most robust defense systems from invasive material. They provide both a physical and chemical barrier between the interior and exterior of the cell. Cellular membranes are complex, containing multitudes of different lipid varieties that assemble into surface features and incorporate membrane proteins that actively perform tasks while contained within the bilayer. Due to this complexity, interactions between native cell membranes and nanoparticles are difficult to characterize when performing whole cell exposure studies. Lipid bilayer model systems simplify the cell membrane down to a handful of molecular components so that fundamental mechanisms of interaction between nanoparticles and lipids can be studied. The work presented here has focused on the simplest variety of model lipid bilayer, the single component lipid bilayer, to allow for rigorous characterization of molecular interactions with nanomaterials. We used the first model system highlighted here, supported lipid bilayers, to understand the interactions between ligand coated gold nanoparticles and cellular membranes. We exposed supported lipid bilayers to 2 nm gold nanoparticles functionalized with ligands of systematically increasing lipophilicity. We found that increasing lipophilicity of ligands increased the maximum mass density of nanoparticle adsorption and the rate at which nanoparticles converted to the quasi-irreversibly adsorbed state. The quasi-irreversibly bound state was linked to ligand insertion, which we define by the ability of a ligand to form hydrophobic contact with lipid tail groups. An issue with previous applications of the supported lipid bilayer system is that it under predicts the interaction of anionic nanoparticles with the membrane when compared to both computational and cellular exposure models. We found that interactions between anionic nanoparticles and supported lipid bilayers are impacted by the composition of the substrate upon which the bilayer is built. Specifically, we find that SiO2-a widely used substrate-hindered the adsorption of anionic gold nanoparticles to the bilayer as compared to a Au substrate. This change is attributed to both the increased attractive van der Waals forces and decreased repulsive Coulombic forces of nanoparticles interacting with bilayers formed on Au vs SiO2 substrates, respectively. A second model membrane system, unilamellar vesicles, has been used to monitor nanomaterial induced disruption or remodeling of lipid bilayers; however, a difficulty when using this model system is the inability to rigorously track the nanomaterial with respect to a disruption or remodeling event, due to the small size dimensions of the nanoparticle. We work to develop a method of tracking both fluorescent vesicles and nanomaterials simultaneously with convex lens induced confinement. The final set of studies presented here utilizes a third model biological system: plant xylem fluid. Nanomaterial based approaches to suppressing plant disease and increasing crop yields are being explored; however, little is known about molecular level interactions between the nanomaterials proposed in this research and the plants. We conducted a set of measurements to understand how copper oxide nanoparticles, a nanomaterial that has shown promise as a micronutrient delivery to plants, interact with the biomolecules found in xylem fluid. We found that proteins from the xylem fluid associate with the nanoparticles, a phenomenon known as biomolecular corona formation. Additionally, we found that protein adsorption is selective to a subset of proteins found within the xylem fluid and the corona evolves over time.0́3

Book Surface Chemistry of Nanobiomaterials

Download or read book Surface Chemistry of Nanobiomaterials written by Alexandru Grumezescu and published by William Andrew. This book was released on 2016-02-03 with total page 530 pages. Available in PDF, EPUB and Kindle. Book excerpt: Surface Chemistry of Nanobiomaterials brings together the most recent findings regarding the surface modification of currently used nanomaterials, which is a field that has become increasingly important during the last decade. This book enables the results of current research to reach those who wish to use this knowledge in an applied setting. Leading researchers from around the world present various types of nanobiomaterials, such as quantum dots (QDs), carbon nanotubes, silver nanoparticles, copper oxide, zinc oxide, magnesium oxide, magnetite, hydroxyapatite and graphene, and discuss their related functionalization strategies. This book will be of interest to postdoctoral researchers, professors and students engaged in the fields of materials science, biotechnology and applied chemistry. It will also be highly valuable to those working in industry, including pharmaceutics and biotechnology companies, medical researchers, biomedical engineers and advanced clinicians. - An up-to-date and highly structured reference source for researchers, practitioners and students working in biomedical, biotechnological and engineering fields - A valuable guide to recent scientific developments, covering major and emerging applications of nanomaterials in the biomedical field - Proposes novel opportunities and ideas for developing or improving technologies in nanomedicine and nanobiology

Book Multiscale Modeling of Particle Interactions

Download or read book Multiscale Modeling of Particle Interactions written by Michael King and published by John Wiley & Sons. This book was released on 2010-03-30 with total page 398 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discover how the latest computational tools are building our understanding of particle interactions and leading to new applications With this book as their guide, readers will gain a new appreciation of the critical role that particle interactions play in advancing research and developing new applications in the biological sciences, chemical engineering, toxicology, medicine, and manufacturing technology The book explores particles ranging in size from cations to whole cells to tissues and processed materials. A focus on recreating complex, real-world dynamical systems helps readers gain a deeper understanding of cell and tissue mechanics, theoretical aspects of multiscale modeling, and the latest applications in biology and nanotechnology. Following an introductory chapter, Multiscale Modeling of Particle Interactions is divided into two parts: Part I, Applications in Nanotechnology, covers: Multiscale modeling of nanoscale aggregation phenomena: applications in semiconductor materials processing Multiscale modeling of rare events in self-assembled systems Continuum description of atomic sheets Coulombic dragging and mechanical propelling of molecules in nanofluidic systems Molecular dynamics modeling of nanodroplets and nanoparticles Modeling the interactions between compliant microcapsules and patterned surfaces Part II, Applications in Biology, covers: Coarse-grained and multiscale simulations of lipid bilayers Stochastic approach to biochemical kinetics In silico modeling of angiogenesis at multiple scales Large-scale simulation of blood flow in microvessels Molecular to multicellular deformation during adhesion of immune cells under flow Each article was contributed by one or more leading experts and pioneers in the field. All readers, from chemists and biologists to engineers and students, will gain new insights into how the latest tools in computational science can improve our understanding of particle interactions and support the development of novel applications across the broad spectrum of disciplines in biology and nanotechnology.

Book Interaction Between Silver Nanoparticles and Model Cell Membranes

Download or read book Interaction Between Silver Nanoparticles and Model Cell Membranes written by Mona Kavianipour and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The use of nanoparticles (NPs) in research and technology is rapidly expanding; NPs have become part of our daily life in medical, cosmetic, or food products. Since exposure of cells to some biofunctional NPs might be fatal if the NPs are toxic, applying NPs with minimal cytotoxicity should be considered. In this study, we investigated the effect of Ag NPs on model cell membranes, namely, suspended unilamellar vesicles (SUVs) using the fluorescent probe, 1-N-phenylnaphthylamine (NPN) that fluoresces in a hydrophobic environment such as the internal region of the lipid bilayer. A multi-well plate reader was used to record fluorescence spectra of neutral, and negatively charged vesicles exposed to different concentrations of NPs; in this technique, a loss in fluorescence intensity corresponds to disruption of the model cell membrane. To provide insight into the fate of Ag NPs and their impact on cell membrane permeability, the interaction of Ag NPs and Ag ions (AgNO3) with two component model membranes (neutral and negatively-charged SUVs) was analyzed. We observed an 83% reduction in the fluorescence intensity of negatively-charged vesicles interacting with 40 mM Ag ions. A lower level of membrane disruption (50% reduction in fluorescence intensity) was observed for the neutrally charged SUVs indicating that electrostatic interactions play an important role. Since the phase behavior of a phospholipid bilayer influences vesicle properties, the effect of temperature was also examined. Furthermore, we investigated the effect of NP surface coating on NP-vesicle interaction as the properties of the NPs can be significantly altered through their surface modification, and we observed different behavior for PVP- and citrate-coated silver NPs. The role of NP type on NP-vesicle interaction was examined using 50-nm-PVP coated gold and silver NPs. Dynamic light scattering was used to measure the size distribution, surface potential of the SUVs, and the likelihood of aggregation over time. The measurements revealed that by increasing the Ag ion concentration, the aggregation of vesicles increased. More SUV aggregation was observed for negatively charged vesicles in comparison to neutral ones. Nanoparticle tracking analysis was also utilized to determine the lipid vesicle size. The amount of dissolved silver was determined for both PVP- and citrate-coated NPs using inductively couple plasma mass spectrometry in a single particle mode. Overall, this study demonstrates a novel approach to study the disruption of model cell membranes by metal ions and NPs. " --

Book Protein Nanoparticle Interactions

Download or read book Protein Nanoparticle Interactions written by Masoud Rahman and published by Springer Science & Business Media. This book was released on 2013-06-24 with total page 95 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, the fabrication of nanomaterials and exploration of their properties have attracted the attention of various scientific disciplines such as biology, physics, chemistry, and engineering. Although nanoparticulate systems are of significant interest in various scientific and technological areas, there is little known about the safety of these nanoscale objects. It has now been established that the surfaces of nanoparticles are immediately covered by biomolecules (e.g. proteins, ions, and enzymes) upon their entrance into a biological medium. This interaction with the biological medium modulates the surface of the nanoparticles, conferring a “biological identity” to their surfaces (referred to as a “corona”), which determines the subsequent cellular/tissue responses. The new interface between the nanoparticles and the biological medium/proteins, called “bio-nano interface,” has been very rarely studied in detail to date, though the interest in this topic is rapidly growing. In this book, the importance of the physiochemical characteristics of nanoparticles for the properties of the protein corona is discussed in detail, followed by comprehensive descriptions of the methods for assessing the protein-nanoparticle interactions. The advantages and limitations of available corona evaluation methods (e.g. spectroscopy methods, mass spectrometry, nuclear magnetic resonance, electron microscopy, X-ray crystallography, and differential centrifugal sedimentation) are examined in detail, followed by a discussion of the possibilities for enhancing the current methods and a call for new techniques. Moreover, the advantages and disadvantages of protein-nanoparticle interaction phenomena are explored and discussed, with a focus on the biological impacts.

Book A Guide to Monte Carlo Simulations in Statistical Physics

Download or read book A Guide to Monte Carlo Simulations in Statistical Physics written by David P. Landau and published by Cambridge University Press. This book was released on 2005-09 with total page 456 pages. Available in PDF, EPUB and Kindle. Book excerpt: This updated edition deals with the Monte Carlo simulation of complex physical systems encountered in condensed-matter physics, statistical mechanics, and related fields. It contains many applications, examples, and exercises to help the reader. It is an excellent guide for graduate students and researchers who use computer simulations in their research.

Book Fundamentals of Sum Frequency Spectroscopy

Download or read book Fundamentals of Sum Frequency Spectroscopy written by Y. R. Shen and published by Cambridge University Press. This book was released on 2016-02-18 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first book on the topic, and written by the founder of the technique, this comprehensive resource provides a detailed overview of sum-frequency spectroscopy, its fundamental principles, and the wide range of applications for surfaces, interfaces, and bulk. Beginning with an overview of the historical context, and introductions to the basic theory of nonlinear optics and surface sum-frequency generation, topics covered include discussion of different experimental arrangements adopted by researchers, notes on proper data analysis, an up-to-date survey commenting on the wide range of successful applications of the tool, and a valuable insight into current unsolved problems and potential areas to be explored in the future. With the addition of chapter appendices that offer the opportunity for more in-depth theoretical discussion, this is an essential resource that integrates all aspects of the subject and is ideal for anyone using, or interested in using, sum-frequency spectroscopy.

Book Physics of Biological Membranes

Download or read book Physics of Biological Membranes written by Patricia Bassereau and published by Springer. This book was released on 2018-12-30 with total page 616 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book mainly focuses on key aspects of biomembranes that have emerged over the past 15 years. It covers static and dynamic descriptions, as well as modeling for membrane organization and shape at the local and global (at the cell level) scale. It also discusses several new developments in non-equilibrium aspects that have not yet been covered elsewhere. Biological membranes are the seat of interactions between cells and the rest of the world, and internally, they are at the core of complex dynamic reorganizations and chemical reactions. Despite the long tradition of membrane research in biophysics, the physics of cell membranes as well as of biomimetic or synthetic membranes is a rapidly developing field. Though successful books have already been published on this topic over the past decades, none include the most recent advances. Additionally, in this domain, the traditional distinction between biological and physical approaches tends to blur. This book gathers the most recent advances in this area, and will benefit biologists and physicists alike.

Book Interactions of Engineered Silica Nanoparticles with Cell Membrane Models

Download or read book Interactions of Engineered Silica Nanoparticles with Cell Membrane Models written by Ali Asghari Adib and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The ubiquity of engineered nanomaterials in industrial and biomedical applications has led to higher chances of exposure, raising concerns regarding their cytotoxicity. In this thesis, interactions of engineered silica nanoparticles (104 ± 5 nm), coated with different surface functional groups [hydroxyl, amine, and polyethylene glycol (PEG) 2K, PEG 5K, PEG 20K], with lipid monolayer and lipid bilayer membrane models are investigated.

Book Polymer Nanoparticles for Nanomedicines

Download or read book Polymer Nanoparticles for Nanomedicines written by Christine Vauthier and published by Springer. This book was released on 2017-01-07 with total page 649 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume serves as a valuable handbook for the development of nanomedicines made of polymer nanoparticles because it provides researchers, students, and entrepreneurs with all the material necessary to begin their own projects in this field. Readers will find protocols to prepare polymer nanoparticles using different methods, since these are based on the variety of experiences that experts encounter in the field. In addition, complex topics such as, the optimal characterization of polymer nanoparticles is discussed, as well as practical guidelines on how to formulate polymer nanoparticles into nanomedicines, and how to modify the properties of nanoparticles to give them the different functionalities required to become an efficient nanomedicine for different clinical applications. The book also discusses the translation of technology from research to practice, considering aspects related to industrialization of preparation and aspects of regulatory and clinical development.

Book Influence of Proteins and Ordered Lipid Domains on Nanoparticle Interactions with Model Biomembranes

Download or read book Influence of Proteins and Ordered Lipid Domains on Nanoparticle Interactions with Model Biomembranes written by Eric S. Melby and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Studies of nanoparticle interaction with model biomembranes can provide important insights into the role of individual biomolecules in governing these interactions that are often not possible in studies with living cells as a result of their biomolecular complexity. That being said, it is important that we balance the simplicity that our model systems can provide with the true complexity of the systems we aim to understand. In this field researchers have focused on understanding the interaction between as-synthesized nanoparticles and model biomembranes composed of a single phospholipid or binary mixtures of phospholipids. While these studies are fundamentally important, it is critical that we simultaneously begin to expand this research in new directions by systematically evaluating how other important membrane structures, membrane biomolecules, and nanoparticle alterations after synthesis may govern nanoparticle interactions with biological systems. In the studies discussed here we have pushed the boundaries of research in this field and demonstrated the dramatic effect that phase-segregated membrane domains, peripheral membrane proteins, and nanoparticles modified by the formation of complexes with proteins can have on nanoparticle interactions with model biomembranes. Taken together these results provide insights into designing studies with nanoparticles and model biomembranes that more closely parallel the interactions between nanoparticles and true cellular membranes. This includes the need to investigate how after-synthesis nanoparticle modifications, such as complexation with proteins and natural organic matter, alter the properties of nanoparticles and ultimately their interactions with biological systems. Furthermore, it highlights the need to carefully consider all membrane biomolecules and the ways in which their presence in the membrane may guide the interactions with nanoparticles, not simply individual phospholipids. Finally, investigations of nanoparticle interaction with model biomembranes that most effectively mimic the interactions with true biological systems should be guided by collaborations that bring together experts in model biomembranes, living cells, and computational simulations. Such collaborations will result in deeper, and more rapid, insights that have the potential to deeply benefit society through the effective use of benign nanoparticles.

Book Molecular Simulations and Biomembranes

Download or read book Molecular Simulations and Biomembranes written by Mark S P Sansom and published by Royal Society of Chemistry. This book was released on 2010-08-01 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: The need for information in the understanding of membrane systems has been caused by three things - an increase in computer power; methodological developments and the recent expansion in the number of researchers working on it worldwide. However, there has been no up-to-date book that covers the application of simulation methods to membrane systems directly and this book fills an important void in the market. It provides a much needed update on the current methods and applications as well as highlighting recent advances in the way computer simulation can be applied to the field of membranes and membrane proteins. The objectives are to show how simulation methods can provide an important contribution to the understanding of these systems. The scope of the book is such that it covers simulation of membranes and membrane proteins, but also covers the more recent methodological developments such as coarse-grained molecular dynamics and multiscale approaches in systems biology. Applications embrace a range of biological processes including ion channel and transport proteins. The book is wide ranging with broad coverage and a strong coupling to experimental results wherever possible, including colour illustrations to highlight particular aspects of molecular structure. With an internationally respected list of authors, its publication is timely and it will prove indispensable to a large scientific readership.

Book Cell and Model Membrane Interactions

Download or read book Cell and Model Membrane Interactions written by S. Ohki and published by Springer. This book was released on 2012-10-23 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane interaction is a large research area involving various disciplines. A symposium entitled "Cell and Model Membrane Interactions" which took place in Boston, MA during the 155th American Chemical Society Meeting, April 25, 1990, focused on membrane adhesion and fusion. The topics were explored in studies involving lipids, virus envelopes and cell membranes. Especially discussed, were the roles of polymers, lipids, and proteins on these membrane interactions. Fusion of membrane is an important molecular event which plays a pivotal role in many dynamic cellular processes, such as exocytosis, endocytosis, membrane genesis, viral infection processes, etc. The process includes adhesion of the mem branes, fusion, and finally reorganization of the components of the two membranes. The basic notion shared during the symposium was that membrane hydro phobicity, especially local membrane hydrophobicity is one of the important factors contributing to membrane fusion. Most of the papers are collected here and they are arranged approximately in the same order as they were presented at the sympo sium. These papers are the most up-to-date and representative work at the forefront in each membrane interaction field. I sincerely hope the reader will gain further understanding on membrane interactions especially, membrane and vesicle fusion phenomena through this symposium proceedings volume.

Book The Role of Lipid Domains and Sterol Chemistry in Nanoparticle cell Membrane Interactions

Download or read book The Role of Lipid Domains and Sterol Chemistry in Nanoparticle cell Membrane Interactions written by Andrew B. Fuhrer and published by . This book was released on 2020 with total page 55 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is a growing interest in the scientific research community to develop nanoparticles for use in novel commercial and biomedical applications, fueled by recent advances in nanotechnology and nanoparticle synthesis. Potential applications for nanoparticles include use as catalysts during chemical manufacturing processes, use as drug delivery vehicles and imaging agents for biomedical applications, and as surfaces for adsorption during removal of environmental pollutants. The use of nanoparticles in such applications has raised questions concerning their safety and impact on human health. Answers to these questions require a greater understanding of the interactions between nanoparticles and living cells. Models of the cell membrane have been employed to investigate how nanoparticles may adsorb to, fuse with, or penetrate the cell membrane, however careful consideration of the membrane model for such mechanistic studies is necessary. This thesis investigates the role of membrane lipid domains, which are lipid phase segregations comprised of saturated lipids and sterols, in modulating nanoparticle-membrane interactions and further explores how sterol chemistry impacts said interaction. Model membranes were synthesized with an equimolar ratio of sphingomyelin, 1,2-dioleoyl-sn-glycero-3-phosphocholine, and varied sterol composition to yield vesicles with varied lipid domain properties. Fluorescence anisotropy and Forster resonance energy transfer of fluorescent probes was measured to quantify the degree of ordered domain formation in model vesicles. Additionally, confocal microscopy was performed to visualize lipid domains. Following lipid domain characterization, vesicles in which a self-quenching fluorescent dye was encapsulated were exposed to plain silica nanoparticles (diameter 37.5 ± 1.8 nm) and leakage of dye was measured to determine the degree of membrane disruption. By analyzing the results of vesicle leakage assays alongside the results from domain characterization, it was concluded that the lipid domain profile of the membrane alone is not an ideal predictor of nanoparticle-membrane interactions

Book Nanoparticle cell Lipid Membrane Biophysical Interaction and Its Role in Developing Tumor Targeted Nanoparticles

Download or read book Nanoparticle cell Lipid Membrane Biophysical Interaction and Its Role in Developing Tumor Targeted Nanoparticles written by Radhika Bhave and published by . This book was released on 2015 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor targeted nanoparticles could improve drug delivery of the encapsulated cancer therapeutics to the tumor while reducing their non-specific side effects. However, complex conjugation chemistry, weak antibody-nanoparticle binding, and finite number of receptors available for nanoparticle binding could limit the efficacy of tumor targeted nanoparticles. Therefore, there is need for a new approach to improve nanoparticle localization in tumors. Physical properties of nanoparticles particularly their surface properties have shown to influence in vitro cellular uptake, in vivo biodistribution and tumor localization of nanoparticles. Apart from physical characteristics of nanoparticles, their uptake has also been shown to depend on the cell type. Additionally, progression of disease such as cancer can cause changes in the cell membrane lipid composition, and thereby influence nanoparticle-cell membrane interactions and cellular uptake of nanoparticles. The research described in this thesis explores an interesting approach that explores the differences in the cell membrane lipid composition as well as modification in nanoparticle surface characteristics to design nanoparticles that would preferentially target tumors.In our study, biophysical interactions between nanoparticles and endothelial cell model membrane demonstrate the effect of surface chemistry of nanoparticles on such interactions. Nanoparticles with sulfate and amine surface chemistry show higher interactions with model membrane as compared to nanoparticles with carboxyl and amidine surface chemistry. Biophysical characteristics of cell membrane lipids extracted from normal endothelial and cancerous cells demonstrate the fluidic nature of cancerous cell membrane as compared to the rigid and condensed nature of normal endothelial cell membrane. Nanoparticle-cell membrane lipid interactions demonstrate more selective interactions between nanoparticles with sulfate surface chemistry and cancer cell membrane lipids than with normal cell membrane lipids. On the other hand, nanoparticles with amine surface chemistry demonstrate non-selective interactions with both cancerous and endothelial cell lipid membranes. Nanoparticles loaded with a hydrophobic near infrared dye were used to quantitatively determine biodistribution and tumor localization of nanoparticles in vivo, using an optical imaging technique. Surface chemistry of nanoparticles was shown to influence nanoparticles biodistribution and tumor localization. Nanoparticles with sulfate groups demonstrate higher tumor localization and retention as compared to nanoparticles with amine and carboxyl groups. The results demonstrate that selectivity of nanoparticle with sulfate surface chemistry towards cancerous cell lipid membrane translates in greater tumor localization in vivo. We further studied effect of surface of PLGA-based biodegradable nanoparticles and their interactions with model membranes. These biodegradable nanoparticles when formulated using emulsion-solvent evaporation method retains a fraction of emulsifier, polyvinyl alcohol (PVA) associated with the surface, commonly referred as residual PVA. In this study, nanoparticles were formulated with PVA of different molecular weight and degree of hydrolysis. Our findings illustrated that surface associated residual PVA significantly influences biophysical interactions of nanoparticles with endothelial cell model membrane. Biophysical interactions between nanoparticles and cell lipid membranes could potentially be explored to understand the effect of surface characteristics of nanoparticles on cellular uptake, biodistribution and targeting.