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Introduction
Publications
Publications (125)
Protein misfolding and aggregation are hallmarks of many diseases, including amyotrophic lateral sclerosis (ALS). In familial ALS, aberrant self-association of mutant Cu,Zn-superoxide dismutase (SOD1) is implicated as a key contributor to disease. Mutations have the largest impacts on the stability of the most immature form of SOD1, the unmetallate...
We have studied the impact of cholesterol and/or melatonin on the static and dynamical properties of bilayers made of DPPC or DOPC utilizing neutron scattering techniques, Raman spectroscopy and molecular dynamics simulations. While differing in the amplitude of the effect due to cholesterol or melatonin when comparing their interactions with the t...
The c subunit is an inner mitochondrial membrane (IMM) protein encoded by three nuclear genes. Best known as an integral part of the F0 complex of the ATP synthase, the c subunit is also present in other cytoplasmic compartments in ceroid lipofuscinoses. Under physiological conditions, this 75 residue-long peptide folds into an α-helical hairpin an...
Developing highly piezoelectric nanoparticles (NPs) with inherent mechanical-electrical coupling effect is critically important for energy harvesters, self-powered sensors and actuators. Over the past decades, the NPs with a high longitudinal piezoelectric coefficient (d33) were developed for piezoelectric nanogenerators (PENGs) that operate under...
In novel gene therapy mechanisms utilising gemini surfactants, electrostatic interactions of the surfactant molecules with the DNA strands is a primary mechanism by which the two components of the delivery vehicle bind. In this work, we show for the first time direct evidence of electrostatic interactions of these compounds visualised with Kelvin p...
Neurodegeneration in Alzheimer’s disease (AD) is defined by pathology featuring amyloid−β (Aβ) deposition in the brain. Aβ monomers themselves are generally considered to be nontoxic, but misfold into β−sheets and aggregate to form neurotoxic oligomers. One suggested strategy to treat AD is to prevent the formation of toxic oligomers. The SG inhibi...
The structure and biophysical properties of lipid membranes are important for cellular functions in health and disease. In Alzheimer’s disease, the neuronal membrane is a target for toxic amyloid-β (Aβ). Melatonin is an important pineal gland hormone that has been shown to protect against Aβ toxicity in cellular and animal studies, but the molecula...
In the modern era, structural health monitoring (SHM) is critically important and indispensable in the aerospace industry as an effective measure to enhance the safety and consistency of aircraft structures by deploying a reliable sensor network. The deployment of built-in sensor networks enables uninterrupted structural integrity monitoring of an...
There is an urgent demand in the industry for the development of compact, flexible, and sustainable power sources for self-powered internet of things (IoT) micro/nano devices. One of the most promising routes is to harness environmental energy through piezoelectric nanogenerators (PNGs). A novel, self-assembled, highly porous perovskite/polymer (po...
Purpose:
To describe the use of Kelvin probe force microscopy (KPFM) to investigate the electrical surface potential of human meibum and to demonstrate successful use of this instrument on both human meibum and a meibum model system (six-lipid stock [6LS]) to elucidate nanoscale surface chemistry and self-assembly characteristics.
Materials and m...
Melatonin is a neurohormone that has been shown to be protective in Alzheimer's diseases against amyloid-β (Aβ) toxicity, which involves interaction of Aβ with neuronal membrane. Non-specific interactions of melatonin with cell membrane may play a physiological role in this process by preserving membrane fluidity. In the brain, melatonin is derived...
The structure and biophysical properties of lipid biomembranes are important for normal function of plasma and organelle membranes, which is essential for proper functioning of living cells. In Alzheimer’s disease (AD) the structure of neuronal membranes becomes compromised by the toxic effect of amyloid- β (A β ) protein which accumulates at neuro...
The c subunit is an inner mitochondrial membrane (IMM) protein and is an integral part of the F0 complex of the ATP synthase. Under physiological conditions, this short 75 residue-long peptide folds into an α-helical hairpin and forms oligomers spanning the lipid bilayer. In addition to its physiological role, the c subunit has been proposed as a k...
Lipid bilayers are fundamental building blocks of cell membranes, which contain the machinery needed to perform a range of biological functions, including cell-cell recognition, signal transduction, receptor trafficking, viral budding, and cell fusion. Importantly, many of these functions are thought to take place in the laterally phase separated r...
The influence of using Polyethylenimine (PEI) in the electron extraction layers (EELs) on the photo-stability of
inverted organic solar cells (OSCs) is investigated. Results show that introducing PEI in the commonly used ZnO
EELs, either mixed in the same layer with the ZnO (ZnO:PEI mixture) or in a separate layer in the form of a
bilayer EEL confi...
Healthcare has advanced significantly, bringing with it longer life expectancies and a growing population of elders who suffer from dementia, specifically Alzheimer’s disease (AD). The amyloid beta (Aβ) peptide has been implicated in the cause of AD, where the peptides undergo a conformational change and form neurotoxic amyloid oligomers which caus...
In this work, we report a methanol-facilitated approach to directly use aqueous Poly(3,4-ethylenedioxythiophene):Poly(styrene sulfonate) (PEDOT:PSS) in the silver/epoxy composites for preparation of highly electrically conductive adhesives (ECAs) and an investigation of the interaction between PEDOT:PSS nano-gels and silver microflakes. PEDOT:PSS n...
Methods:
Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD). In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid- treatment for 24 h decreased...
Amyloid-beta peptides (Aβ), implicated in Alzheimer’s disease (AD), interact with the cellular membrane and induce amyloid toxicity. The composition of cellular membranes changes in aging and AD. We designed multi-component lipid models to mimic healthy and diseased states of the neuronal membrane. Using atomic force microscopy (AFM), Kelvin probe...
By combining MD simulations and AFS experimental technique, we demonstrated a powerful approach for rational design and single molecule testing of novel inhibitor molecules which can block amyloid-amyloid binding - the first step of toxic amyloid oligomer formation. We designed and tested novel pseudo-peptide amyloid-β (Aβ) inhibitors that bind to...
Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (A\b{eta}) and the inability of A\b{eta} peptides to be cleared from t...
The field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-β from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most in...
The field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-β from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most in...
The molecular arrangement of lipids and proteins within biomembranes and monolayers gives rise to complex film morphologies as well as regions of distinct electrical surface potential, topographical and electrostatic nanoscale domains. To probe these nanodomains in soft matter is a challenging task both experimentally and theoretically. This work a...
The presence of trace concentrations of metallic ions, such as copper and zinc, has previously been shown to drastically increase the aggregation rate and neurotoxicity of amyloid-β (Aβ), the peptide implicated in Alzheimer's disease (AD). The mechanism of why copper and zinc accelerate Aβ aggregation is poorly understood. In this work, we use sing...
Since the invention of the atomic force microscope (AFM) in 1986, there has been a drive to apply this scanning probe technique or a form of this technique to various disciplines in nanoscale science. Magnetic force microscopy (MFM) is a member of a growing family of scanning probe methods and has been widely used for the study of magnetic material...
Piezoelectric nanogenerators (NGs) based on vertically aligned InN nanowires (NWs) are fabricated, characterized, and evaluated. In these NGs, arrays of p-type and intrinsic InN NWs prepared by plasma-assisted molecular beam epitaxy (MBE) demonstrate similar piezoelectric properties. The p-type NGs show 160% more output current and 70% more output...
Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (Aβ) and the inability of Aβ peptides to be cleared from the brain, re...
Purpose:
The purpose of this exploratory study was to investigate the differences in meibomian gland secretions, contact lens (CL) lipid extracts, and CL surface topography between participants with and without meibomian gland dysfunction (MGD).
Methods:
Meibum study: Meibum was collected from all participants and studied via Langmuir-Blodgett (...
Purpose:
The purpose of this study was to use atomic force microscopy to compare and characterize the cleaning abilities of a hydrogen peroxide-based system (HPS) and a polyhexamethylene biguanide-containing multipurpose solution (MPS) at removing in vitro deposited tear film constituents, as well as to determine deposition patterns on various sil...
A pulmonary surfactant (PS) is a thin lipid-protein film covering the surface of the lung alveoli at the air/liquid interface. The primary purpose of a PS is to control the surface tension of the air/liquid interface and to reduce the work of breathing. High levels of cholesterol in a PS are associated with life-threatening acute respiratory distre...
Superparamagnetic iron oxide nanoparticles (SPIONs), due to their controllable sizes, relatively long
in vivo half-life and limited agglomeration, are ideal for biomedical applications such as magnetic
labeling, hyperthermia cancer treatment, targeted drug delivery and for magnetic resonance imaging
(MRI) as contrast enhancement agents. In order to...
Superparamagnetic iron oxide nanoparticles (SPIONs), due to their controllable sizes, relatively long in vivo half-life and limited agglomeration, are ideal for biomedical applications such as magnetic labeling, hyperthermia cancer treatment, targeted drug delivery and for magnetic resonance imaging (MRI) as contrast enhancement agents. In order to...
Metal ions, including copper and zinc, have been implicated in the pathogenesis of Alzheimer's disease through a variety of mechanisms including increased amyloid-β affinity and redox effects. Recent reports have demonstrated that the amyloid-β monomer does not necessarily travel through a definitive intermediary en-route to a stable amyloid fibril...
We performed single molecule dynamic force spectroscopy experiments to study the dimerization of two amyloid-β (1-42) peptides and compared three different theoretical models used to fit experimental data: Bell-Evans, Dudko-Hummer-Szabo, and Friddle-De Yoreo. Using these models we extracted values of the dissociation rate at zero force, k0, and hei...
Abstract Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by dementia and memory loss for which no cure or effective prevention is currently available. Neurodegeneration in AD is linked to formation of amyloid plaques found in brain tissues of Alzheimer's patients during post-mortem examination. Amyloid plaques are...
Melatonin is a pineal hormone that has been shown to have protective effects in several diseases that are associated with cholesterol dysregulation, including cardiovascular disease, Alzheimer's disease, and certain types of cancers. Cholesterol is a major membrane constituent with both a structural and functional influence. It is also known that m...
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by dementia and memory loss for which no cure or preventative strategy is currently available. AD is linked to the formation of amyloid plaques commonly found in the brain of Alzheimer's patients during post-mortem analysis. Amyloid plaques found on the neuronal cell...
Melatonin is a pineal hormone that has been shown to have protective effects in several diseases that are associated with cholesterol dysregulation, including cardiovascular disease, Alzheimer's disease, and certain types of cancers. Cholesterol is a major membrane constituent with both a structural and functional influence. It is also known that m...
Purpose: Beagle dogs develop a form of Alzheimer’s disease (AD), Cognitive Dysfunction Syndrome, with symptoms similar to the disease in humans. We wished to determine the differences in expression of amyloid β between the retinas of cognitively impaired dogs and cognitively normal dogs; to characterize deposits and to compare the results to data p...
The cell membrane plays an important role in the molecular mechanism of amyloid toxicity associated with Alzheimer's disease. The membrane's chemical composition and the incorporation of small molecules, such as melatonin and cholesterol, can alter its structure and physical properties, thereby affecting its interaction with amyloid peptides. Both...
The activation of genomic signaling in response to stressor-mediated cortisol elevation has been extensively studied in teleosts. However, very little is known about the rapid signaling events elicited by this steroid. We tested the hypothesis that cortisol modulates key stress-related signaling pathway in response to an acute stressor in fish live...
The link between metals, Alzheimer's disease (AD) and its implicated protein, amyloid-β (Aβ), is complex and highly studied. AD is believed to occur as a result of the misfolding and aggregation of Aβ. The dyshomeostasis of metal ions and their propensity to interact with Aβ has also been implicated in AD. In this work, we use single molecule atomi...
Cell membranes are typically very complex, consisting of a multitude of different lipids and proteins. Supported lipid bilayers are widely used as model systems to study biological membranes. Atomic force microscopy and force spectroscopy techniques are nanoscale methods that are successfully used to study supported lipid bilayers. These methods, e...
The cell membrane plays an important role in the molecular mechanism of amyloid toxicity associated with Alzheimer's disease. The membrane's chemical composition and the incorporation of small molecules, such as melatonin and cholesterol, can alter its structure and physical properties, thereby affecting its interaction with amyloid peptides. Both...
Kelvin Probe Force Microscopy (KPFM) is a type of scanning probe microscopy which specifically addresses electrostatic properties of materials and has a great potential to bring new discoveries in biomedical research, but currently has limited biological applications.In this work, we report one of a very few applications of Kelvin probe force micro...
Dopamine is a "sticky" biomolecule containing the typical functional groups of mussel adhesive proteins. It can self-polymerize into a nanoscale thin film on various surfaces. We investigated the surface, adhesion, friction and cracking properties of polydopamine (PDA) thin films for their effective transfer to functional devices and biocompatible...
Pulmonary surfactant is a complex mixture of phospholipids and proteins and forms a thin film at the lung alveolar interface separating air from liquid environment. The film reduces the work of breathing during repeatable compressions of the alveoli which form a characteristic multilayer upon compression. In this work, we investigated the structure...
Stress-induced glucocorticoid elevation is a highly conserved response among vertebrates. This facilitates stress adaptation and the mode of action involves activation of the intracellular glucocorticoid receptor leading to the modulation of target gene expression. However, this genomic effect is slow acting and, therefore, a role for glucocorticoi...
Effect of cortisol, RU486, benzyl alcohol & DMSO on membrane fluidity. Anisotropy of isolated hepatic membranes with cortisol (1 µM) RU486 (1 µM) combination treatment (RU+CORT; both 1 µM) benzyl alcohol (BOH; 5 mM), dimethyl sulphoxide (DMSO, 2% v/v) or without (control) at both 4°C and 23°C. Values are shown as % control and bars represent means...
Amyloid fibrils are associated with multiple neurodegenerative disorders, such as Alzheimer's disease. Although biological membranes are involved in fibril plaque formation, the role of lipid membrane composition in fibril formation and toxicity is not well understood. We investigated the effect of cholesterol on the interaction of model lipid memb...
of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.
A new technique, that involves the plasma processing of frozen hydrocarbons by a pulsed laser generated graphitic plasma, is presented. Polymer-like hydrogenated amorphous carbon (a-C:H) thin films were created by allowing the plasma generated during the fs-pulsed laser ablation of a highly oriented pyrolytic graphite target in high vacuum, to impa...
