Vito FoderàUniversity of Copenhagen · Department of Pharmacy
Vito Foderà
PhD in Physics
About
35
Publications
7,085
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Citations
Introduction
Key Scientific Interests:
-Large Scale Amyloid Polymorphism and Superstructures
-Protein Aggregation and Biological Membranes
-UV-Vis Spectroscopy of Dyes for Biological Applications
-Polymeric Hydrogels for Drug Delivery
-Electron Transfer in Biological Samples
Please visit:
http://www.vitofodera.com/
http://pharmacy.ku.dk/research/biologics/protein-formulation-and-biophysics/
Additional affiliations
November 2016 - present
March 2014 - October 2016
September 2012 - August 2014
Education
January 2006 - December 2008
November 1999 - July 2005
Publications
Publications (35)
The conversion of proteins into amyloid fibrils and other amyloid-like aggregates is closely connected to the onset of a series of age-related pathologies. Upon changes in environmental conditions amyloid-like aggregates may also undergo disassembly into oligomeric aggregates, the latter being recognized as key effectors in toxicity. This indicates...
Evaluating the toxicity of self-assembled protein states is a key step towards developing effective strategies against amyloidogenic pathologies as Alzheimer's and Parkinson's diseases. Such analysis is directly connected to quantitatively probing the stability of the cellular membrane upon interaction with different protein states. Using a combina...
Depending on external conditions, native proteins may change their structure and undergo different association routes leading to large scale polymorphism of the aggregates. This feature has been widely observed but is not fully understood yet. This review focuses on morphologies, physico-chemical features and mechanisms of formation of amyloid stru...
Formation of superstructures in protein aggregation processes has been indicated as a general pathway for several proteins, possibly playing a role in human pathologies. There is a severe lack of knowledge on the origin of such species in terms of both mechanisms of formation and structural features. We use equine lysozyme as a model protein, and b...
The subtle interplay between long range electrostatic forces, hydrophobic interactions and short range protein–protein interactions regulates the onset/evolution of protein aggregation processes as well as the stability of protein supramolecular structures. Using a combination of FTIR spectroscopy, light scattering and advanced imaging, we present...
The reliable preparation of functional, ordered, nanostructured frameworks would be a game changer for many emerging technologies, from energy storage to nanomedicine. Underpinned by the excellent molecular recognition of nucleic acids, along with their facile synthesis and breadth of available functionalizations, DNA Nanotechnology is widely ackno...
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The reliable preparation of functional, ordered, nanostructured frameworks would be a game changer for many emerging technologies, from energy storage to nanomedicine. Underpinned by the excellent molecular recognition of nucleic acids, along with their facile synthesis and breadth of available functionalizations, DNA Nanotechnology is widel...
DNA nanostructures with programmable shape and interactions can be used as building blocks for the self-assembly of crystalline materials with prescribed nanoscale features, holding a vast technological potential. Structural rigidity and bond directionality have been recognised as key design features for DNA motifs to sustain long-range order in 3D...
Protein self-assembly into amyloid fibrils or highly hierarchical superstructures is closely linked to neurodegenerative pathologies as Alzheimer’s and Parkinson´s diseases. Moreover, protein assemblies also emerged as building blocks for bio-inspired nanostructured materials. In both the above mentioned fields the main challenge is to control the...
Co-solutes, such as sugars, are used in in vitro protein aggregation experiments to mimic crowding and, in general, complex environments. Sugars often increase the stability of the native protein structure by affecting inter- and intramolecular protein–protein interactions. This, in turn, modifies the protein self-assembly pathways. Using a combina...
Protein fibrillation is the pathological hallmark of several neurodegenerative diseases and also complicates the manufacturing and use of protein drugs. As a case study, the inhibitory activity of the natural compound aloin against insulin fibrillation was investigated. Based on Thioflavin T assays, high-performance liquid chromatography and transm...
Aggregation of proteins into amyloid deposits is the hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations of pre-fibrillar oligomers, which are complicated by their transient nature and low population. He...
Penetratin is a widely used carrier peptide showing promising potential for mucosal delivery of therapeutic proteins. In the present study, the importance of specific penetratin residues and pH was investigated with respect to complexation with insulin and subsequent transepithelial insulin permeation. Besides penetratin, three analogues were studi...
In this chapter we discuss the possibility for proteins to self-assemble in large-scale amyloid aggregates of spherical shape termed amyloid spherulites. Under specific experimental conditions, amyloid spherulites are recognized as a significant component occurring in several protein model systems used for in vitro fibrillation studies. The state o...
Amyloid formation is associated with neurodegenerative diseases such as Parkinson's disease (PD). Significant α-synuclein (αSN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including the molecular mechanisms behind potential amyloid-mediated tox...
Oxidative damages are linked to several aging-related diseases and are among the chemical pathways determining protein degradation. Specifically, interplay of oxidative stress and protein aggregation is recognized to have a link to the loss of cellular function in pathologies like Alzheimer's and Parkinson's diseases. Interaction between protein an...
The possibility for proteins to aggregate in different superstructures, i.e. large-scale polymorphism, has been widely observed, but an understanding of the physicochemical mechanisms behind it is still out of reach. Here we present a theoretical model for the description of a generic aggregate formed from an ensemble of charged proteins. The model...
Understanding the mechanism behind protein aggregation is a challenging task that requires a combined use of both experimental and computational approaches. In this work, we present a 2D model for the formation of amyloid-like fibrils. The model allows to explicitly consider the structural change of the native state of a protein into the aggregatio...
Understanding the early events during amyloid aggregation processes is crucial to single out the involved molecular mechanisms and for designing ad hoc strategies to prevent and reverse amyloidogenic disorders. Here, we show that, in conditions in which the protein is positively charged and its conformational flexibility is enhanced, Concanavalin A...
Amyloid fibrils are characterized by a structural arrangement of cross β-sheet as a common motif. However they can also experience a more complicated packing into a variety of 3D supramolecular structures (polymorphism). Confinement and flow rate play a crucial role in protein aggregation in living systems, but controlling such parameters during in...
Unlabelled:
Extra virgin olive oil (EVOO) is recognized as one of the healthiest foods for its high content of antioxidants, which forestall and slow down radical formation. Free radical-initiated oxidation is considered one of the main causes of rancidity in fats and oils. As a consequence, reliable protocols for the investigation of oil oxidatio...
Thermally induced amyloid aggregation of bovine insulin can produce a number of distinct aggregate morphologies. In this work amyloid spherulites were analysed using cross polarized optical microscopy and light scattering. A new semi-quantitative methodology to estimate the balance of spherulites and free fibrils is reported and, from this analysis...
In the recent years recombinant technology has identified numerous protein based therapeutics. Their
effective delivery, though, can be challenging due to the poor stability of most proteins along their pathway
to the target site in the body. Hydrogels have been identified as good candidates for protein encapsulation
and delivery thanks to both mat...
Aggregation processes, and in general the physical and chemical instability of proteins, are at the moment a major problem related to different scientific fields, spanning from biochemistry and biophysics to pharmaceutical and medical sciences. In fact, increased knowledge on protein aggregation may clarify different aspects related to several dege...
The analysis of amyloidogenic systems reveals the appearance of distinct states of aggregation for amyloid fibrils. For different proteins and under specific experimental conditions, amyloid spherulites are recognized as a significant component occurring in several protein model systems used for in vitro fibrillation studies. In this work we have d...
Under specific conditions the protein hormone insulin is prone to form amyloid fibrils and is widely
used as a model system to study fibril formation mechanisms. In this work we studied thermally
induced fibril formation of insulin in acidic solutions. We mainly focused on the effect of the initial
protein concentration on the final fibril morpholo...
Poly(N-vinyl-2-pyrrolidone) (PVP) hydrogels have been synthesised from the aqueous solutions of the
same linear polymer by two different radiation sources: electron beams and UV rays. The present investigation couples conventional hydrogel characterisation techniques with the study of the partition equilibria, fluorescence behaviour and release of...
At high temperature and low pH, the protein hormone insulin is highly prone to form amyloid fibrils, and for this reason it is widely used as a model system to study fibril formation mechanisms. In this work, we focused on insulin aggregation mechanisms occurring in HCl solutions (pH 1.6) at 60 degrees C. By means of in situ Thioflavin T (ThT) stai...
The fluorescent dye thioflavin T (ThT) is commonly used for in situ amyloid fibril detection. In this work, we focused on the spectroscopic properties and chemical stability of ThT in aqueous solution as a function of pH, temperature, and dye concentration. A reversible hydroxylation process occurs in alkaline solutions, which was characterized usi...
The study of the aggregation processes in presence of metal ions is an essential step for understanding the key role of metals in protein-protein and protein-solvent interactions. Indeed, the presence of metal ions can radically change the main features of the standard denaturation/aggregation processes and such effects result to be strongly depend...
At low pH insulin is highly prone to self-assembly into amyloid fibrils. The process has been proposed to be affected by the existence of secondary nucleation pathways, in which already formed fibrils are able to catalyze the formation of new fibrils. In this work, we studied the fibrillation process of human insulin in a wide range of protein conc...
Insulin, a 51-residue protein universally used in diabetes treatment, is known to produce amyloid fibrils at high temperature and acidic conditions. As for other amyloidogenic proteins, the mechanisms leading to nucleation and growth of insulin fibrils are still poorly understood. We here report a study of the fibrillation process for insulin confi...
Projects
Project (1)
An experimental study, by different techniques at the state of art, to investigate the different mechanisms (conformational and structural changes at single protein level, nucleation processes and protein-protein interactions with consequent formation of new intermolecular bonds) involved in the aggregation processes of proteins. These mechanisms acting on different temporal and spatial scales may evolve in several phases being interconnected. Under specific destabilizing conditions, all proteins seem to have the ability to "misfold" and subsequently assemble themselves in ordered supramolecular aggregates known as amyloid fibrils. Amyloid fibril formation appears to be a fundamental event in the etiology of different pathologies (amyloidoses) such as Parkinson's, Alzheimer's and Creutzfeldt-Jacob disease. In fact, all these pathologies are related to enormous extracellular deposition of amyloid fibrils.
During fibrils formation, different intermediate species, like small oligomers or protofibrils, are commonly observed. It was suggested that the structural order increases from oligomers to protofibrils to fibrils. The mechanisms underlying the growth of amyloid fibrils represent one of the crucial points that need to be clarified also in relation whit their biomedical implication.
