Fibril Axis Research Articles

Coaggregation of κ-Casein and β-Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils.

The unfolding, misfolding, and aggregation of proteins lead to a variety of structural species. One form is the amyloid fibril, a highly aligned, stable, nanofibrillar structure composed of β-sheets running perpendicular to the fibril axis. β-Lactoglobulin (β-Lg) and κ-casein (κ-CN) are two milk proteins that not only individually form amyloid fibrillar aggregates, but can also coaggregate under environmental stress conditions such as elevated temperature. The aggregation between β-Lg and κ-CN is proposed to proceed via disulfide bond formation leading to amorphous aggregates, although the exact mechanism is not known. Herein, using a range of biophysical techniques, it is shown that β-Lg and κ-CN coaggregate to form morphologically distinct co-amyloid fibrillar structures, a phenomenon previously limited to protein isoforms from different species or different peptide sequences from an individual protein. A new mechanism of aggregation is proposed whereby β-Lg and κ-CN not only form disulfide-linked aggregates, but also amyloid fibrillar coaggregates. The coaggregation of two structurally unrelated proteins into cofibrils suggests that the mechanism can be a generic feature of protein aggregation as long as the prerequisites for sequence similarity are met.

Nanomechanical Properties of Polymorphic Human Islet Amyloid Polypeptide Protofibrils in the Multiple Physiological and Mechanical Conditions

Fibrillar and oligomeric amyloids are the origin of neuro-degenerative and degenerative diseases as type II diabetes, Alzheimer's diseases, and so forth. The common properties of amyloids are located near functional cells, not easily degraded, and disrupt their own functions. These amyloids had polymorphic characteristics under physiological conditions such as thermal effect, pH, ionic strength, metal ions and internal fluctuations. Developed from denatured and misfolded amyloid monomers, polymorphic amyloids are mainly existed as parallel or antiparallel composition along to fibril axis and lateral thickness composition by adding unit amyloid protofilament through the experimental techniques. Despite experimental effort of polymorphic structures of amyloid proteins, there are some lacks of knowledge that relationship between structural composition of polymorphic amyloids and their stabilities in detail. The mechanical characterization as bending, stretching can give insight for understanding the structure-property relationship of amyloid protofilaments. Considering that amyloids are developed through the repetitive fragmentation and elongation mechanisms, it is crucial to understand the structural stabilities of polymorphic amyloid protofibrils. Here, we reported the polymorphic characteristics of hIAPP amyloid protofibrils in mechanical insight via equilibrium and steered molecular dynamics (MD and SMD). Through the principal component analysis of polymorphic hIAPP protofibrils after equilibrium MD simulations, we found the different deformation mode (i.e. bending, stretching and torsion) of polymorphic hIAPP protofibrils. Using eigenvalue analysis, antiparallel models had considerable structural stability than parallel models due to the asymmetric hydrogen bond network composition. Furthermore, by applying the constant force bending and constant velocity tensile SMD simulations, we found the dominant material characteristics that homo composition had ductile feature, while hetero composition had brittle characteristics. We provide the relationship between structural composition and their properties, which are related to growth mechanism of amyloids. Our study also provides the possibilities for the basic template for functional biomaterials in the future.

Aggregation behavior of novel heptamethine cyanine dyes upon their binding to native and fibrillar lysozyme.

Two newly synthesized symmetrical heptamethine cyanine dyes, AK7-5 and AK7-6, absorbing in the region of low autofluorescence of biological samples, have been tested for their ability to detect proteins aggregated into amyloid fibrils. In aqueous solution these probes possess three absorption bands corresponding to the monomer, dimer and H-aggregate species. The association of the dye with fibrillar lysozyme was followed by the enhancement of the monomer band and the reduction of the H-band. The absorption spectra measured at various fibril concentrations were analyzed in terms of the model allowing for the shift of equilibria between various dye species due to the binding of monomers and dimers of AK7-5 and AK7-6 to amyloid fibrils. The association constants and stoichiometries of the dye-fibril complexation have been evaluated. In contrast to fibrillar lysozyme, the native protein brought about strong J-aggregate formation accompanied by a marked drop in the absorbance of the dye monomer species. Quantum chemical calculations and simple docking studies showed that AK7-5 and AK7-6 monomers can bind to the grooves, running parallel to the fibril axis. Due to their ability to distinguish between the native and fibrillar protein states, the novel cyanines are recommended as complementary to existing amyloid markers.

AURAMINE O AS POTENTIAL AMYLOID MARKER: FLUORESCENCE AND MOLECULAR DOCKING STUDIES

The applicability of Auramine O to the detection and characterization of lysozyme and serum albumin amyloid fibrils has been assessed using the fluorimetric titration and molecular docking. The parameters of the dye binding to native and fibrillar proteins were estimated in terms of the Langmuir adsorption model. It was found that Auramine O displays the high affinity for amyloid fibrils, being of the same order of magnitude as that of the classical amyloid markers. The dye also showed greater fluorescence response to lysozyme fibrils and lower sensitivity to the native protein, than Thioflavin T. Furthermore, unlike Thioflavin T, Auramine O was able to detect the morphological differences between lysozyme and albumin fibrils due to the shifts in the position of the emission maxima of the fibril-incorporated fluorophore. The molecular docking studies revealed that Auramine O and Thioflavin T form the most stable complexes with the G54_L56/S60_W62 groove of lysozyme fibrils, running parallel to the fibril axis. The results obtained suggest the contribution of both hydrophobic and electrostatic interactions to the stabilization of the dye complexes with amyloid fibrils.

Structural and fluctuational difference between two ends of Aβ amyloid fibril: MD simulations predict only one end has open conformations.

Aβ amyloid fibrils, which are related to Alzheimer’s disease, have a cross-β structure consisting of two β-sheets: β1 and β2. The Aβ peptides are thought to be serially arranged in the same molecular conformation along the fibril axis. However, to understand the amyloid extension mechanism, we must understand the amyloid fibril structure and fluctuation at the fibril end, which has not been revealed to date. Here, we reveal these features by all-atom molecular dynamics (MD) simulations of Aβ42 and Aβ40 fibrils in explicit water. The structure and fluctuation were observed to differ between the two ends. At the even end, the Aβ peptide always took a closed form wherein β1 and β2 were closely spaced. The Aβ peptide fluctuated more at the odd end and took an open form wherein the two β-sheets were well separated. The differences are attributed to the stronger β-sheet formation by the β1 exposed at the even end than the β2 exposed at the odd end. Along with the small fluctuations at the even end, these results explain why the fibril extends from one end only, as observed in experiments. Our MD results agree well with recent observations by high-speed atomic force microscopy.

Few Ramachandran Angle Changes Provide Interaction Strength Increase in Aβ42 versus Aβ40 Amyloid Fibrils.

The pathology of Alzheimer’s disease can ultimately be traced to the increased aggregation stability of Aβ42 peptides which possess two extra residues (Ile 41 & Ala 42) that the non-pathological strain (Aβ40) lacks. We have found Aβ42 fibrils to exhibit stronger energies in inter-chain interactions and we have also identified the cause for this increase to be the result of different Ramachandran angle values in certain residues of the Aβ42 strain compared to Aβ40. These unique angle configurations result in the peptide planes in the fibril structures to be more vertical along the fibril axis for Aβ42 which thus reduces the inter-atomic distance between interacting atoms on vicinal peptide chains thereby increasing the electrostatic interaction energies. We lastly postulate that these different Ramachandran angle values could possibly be traced to the unique conformational folding avenues sampled by the Aβ42 peptide owing to the presence of its two extra residues.

Determination of the elastic modulus of β-lactoglobulin amyloid fibrils by measuring the Debye-Waller factor

Although amyloid fibrils are associated with amyloidoses, they are now being considered as novel biomaterials for industrial use due to their structural stability in the matured state. Therefore, the physical characteristics of these materials need to be clarified prior to their industrial application. In the present study, the mechanical properties of amyloid fibrils precursored by β-lactoglobulin were investigated. Previous studies have examined the stiffness or modulus values of these fibrils using atomic force microscopy. However, the modulus values reported, even for amyloid fibrils from the same precursor proteins, range over three orders of magnitude, from a few MPa to GPa, depending on the experimental methods employed under specific loading conditions. We determined the elastic modulus of amyloid fibrils by measuring spontaneous thermal fluctuations in the material, the Debye-Waller factor. This method does not require any contact between the probe and material or any loading. The vibrational modes of a fibril were considered in order to estimate mechanical parameters. The modulus value determined along the fibril axis for single amyloid fibrils was slightly smaller than those reported in the literature. The smaller modulus value suggests the existence of less ordered proto-fibrils in our specimen, which was confirmed by the AFM images.

Molecular Mechanism of Polarization and Piezoelectric Effect in Super-Twisted Collagen.

It has been known for decades that bone exhibits piezoelectric behavior. In recent years, it was directly proved that this effect stems from a polymeric matrix in bone, i.e., collagen fibrils. This effect in collagen is distinctly different from organic piezoelectric crystals, given the semicrystalline molecular structure of the collagen biopolymer. As such, the molecular mechanism of this electromechanical coupling effect in a realistic "super-twisted" model of collagen has been elusive. Herein, we present an investigation on the molecular mechanism of piezoelectric effect in collagen using full atomistic simulation based on the experimentally verified "super-twisted" microstructure of collagen. Our results reveal that collagen exhibits a uniaxial polarization along the long axis of the collagen fibril. In addition, the piezoelectric effect in collagen originates at the collagen molecule level and is due to the mechanical stress-induced reorientation and magnitude change of the permanent dipoles of individual charged and polar residues. A piezoelectric constant in the range of 1-2 pm/V (pC/N) is obtained from the simulation, which agrees well with the experimental data.

How Do the Size, Charge and Shape of Nanoparticles Affect Amyloid β Aggregation on Brain Lipid Bilayer?

Here, we studied the effect of the size, shape, and surface charge of Au nanoparticles (AuNPs) on amyloid beta (Aβ) aggregation on a total brain lipid-based supported lipid bilayer (brain SLB), a fluid platform that facilitates Aβ-AuNP aggregation process. We found that larger AuNPs induce large and amorphous aggregates on the brain SLB, whereas smaller AuNPs induce protofibrillar Aβ structures. Positively charged AuNPs were more strongly attracted to Aβ than negatively charged AuNPs, and the stronger interactions between AuNPs and Aβ resulted in fewer β-sheets and more random coil structures. We also compared spherical AuNPs, gold nanorods (AuNRs), and gold nanocubes (AuNCs) to study the effect of nanoparticle shape on Aβ aggregation on the brain SLB. Aβ was preferentially bound to the long axis of AuNRs and fewer fibrils were formed whereas all the facets of AuNCs interacted with Aβ to produce the fibril networks. Finally, it was revealed that different nanostructures induce different cytotoxicity on neuroblastoma cells, and, overall, smaller Aβ aggregates induce higher cytotoxicity. The results offer insight into the roles of NPs and brain SLB in Aβ aggregation on the cell membrane and can facilitate the understanding of Aβ-nanostructure co-aggregation mechanism and tuning Aβ aggregate structures.

Spin Labeling and Characterization of Tau Fibrils Using Electron Paramagnetic Resonance (EPR).

Template-assisted propagation of Tau fibrils is essential for the spreading of Tau pathology in Alzheimer's disease. In this process, small seeds of fibrils recruit Tau monomers onto their ends. The physical properties of the fibrils play an important role in their propagation. Here, we describe two different electron paramagnetic resonance (EPR) techniques that have provided crucial insights into the structure of Tau fibrils. Both techniques rely on the site-directed introduction of one or two spin labels into the protein monomer. Continuous-wave (CW) EPR provides information on which amino acid residues are contained in the fibril core and how they are stacked along the long fibril axis. Double electron-electron resonance (DEER) determines distances between two spin labels within a single protein and hence provides insights into their spatial arrangement in the fibril cross section. Because of the long distance range accessible to DEER (~2-5 nm) populations of distinct fibril conformers can be differentiated.

The effect of polyaspartate chain length on in vitro remineralization of dental tissues

Event Abstract Back to Event The effect of polyaspartate chain length on in vitro remineralization of dental tissues Bryan Quan1 and Eli D. Sone1, 2, 3 1 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada 2 University of Toronto, Faculty of Dentistry, Canada 3 University of Toronto, Department of Materials Science & Engineering, Canada Introduction: Most mineralized mammalian tissues are composites of hydroxyapatite (HAP) and collagen fibrils, with between 10 % and 80 % of bone and dentin HAP estimated to be intrafibrillar. Though intrafibrillar HAP is essential to the mechanical properties of bony tissues, the mechanism of intrafibrillar mineralization is not well known. However, it is thought that mineralizing proteins are involved in directing the process. These proteins are typically enriched in aspartate or glutamate residues[1], which is important for their mineralization-regulating properties[2]. Recently polyaspartate (pAsp) and polyacrylate, used as analogs of mineralizing proteins, have been shown to mediate intrafibrillar HAP formation in spontaneously precipitating calcium-phosphate (CaP) solutions[3]. Currently, the roles of these polycarboxylate additives and the parameters which govern their effectiveness are not well described. Here, we investigate the effect of pAsp chain length on remineralization of dental tissues and characterize the remineralizing solutions to gain insight into the mechanisms of intrafibrillar mineralization. These studies will lead to improved materials for fixation, replacement, and repair of bony tissues. Materials and Methods: We remineralize ultrathin sections of demineralized mouse dental tissues directly on TEM grids in spontaneously precipitating solutions of calcium and phosphate ions[4], using either no pAsp as a control, or low polydispersity pAsp additives with nominal degrees of polymerization (DP) of 6, 10, and 100 to mediate intrafibrillar remineralization. Remineralization outcomes are characterized by conventional transmission electron microscopy (TEM), while the remineralizing solutions are characterized by a combination of Ca2+-ion selective electrode (ISE) measurements, dynamic light scattering (DLS), and TEM. Results and Discussion: Remineralization experiments (Figure 1) show that with no pAsp, or with pAsp hexapeptide, superficial HAP forms quickly and without selectivity, while selected area electron diffraction (SAED) indicates no preferential HAP orientation. Conversely, pAsp with DP 10 or 100 induces selective remineralization of only the natively mineralizing tissues dentin and cementum, and SAED of shows that the c-axes of HAP crystals orient with the long axes of collagen fibrils. This demonstrates a role for both pAsp and tissue-specific mineralization factors in determining mineralization selectivity. Though the affinity of pAsp for Ca2+ is relatively insensitive to DP, ISE measurements show that higher DP pAsp better inhibits crystallization, while DLS suggests that a higher DP pAsp better inhibits the formation of amorphous CaP precursors (not shown). These results suggest that pAsp inhibits CaP precipitation in the solution compartment, thereby maintaining a high supersaturation and supporting intrafibrillar mineralization. Conclusion: We show that while higher DP pAsp is an effective mediator of intrafibrillar mineralization, pAsp with DP 6 is not. However, pAsp with DP as low as 10 does mediate intrafibrillar mineralization. This demonstrates a lower size limit for the effective inhibition of amorphous CaP formation and CaP crystallization in solution by aspartate repeats in mineralizing proteins. Figure 1 - TEM micrographs and SAED of sections remineralized in solution control (a) or with 25μg/mL pAsp6 (b), pAsp10 (c), or pAsp100 (d).

Detection of amyloid-β fibrils using the DNA-intercalating dye YOYO-1: Binding mode and fibril formation kinetics

Identification of the chemical and biological properties of amyloid fibrils is important for understanding their roles in human diseases and to clarify the mechanisms that govern their formation. In pursuit of these goals, small molecule fluorescent dyes have received increasing attention as probes of amyloid conformations. In this study, we report on the ability of YOYO-1, a homodimeric derivative of oxazole yellow, to detect fibrils formed by the Alzheimer's disease related Aβ(1–42) peptide. We find that YOYO-1 binds to Aβ(1–42) fibrils with the long axes of its oxazole yellow moieties parallel to the fibril axis, resulting in a 200x emission enhancement; a result that shows that YOYO-1 is a sensitive amyloid probe. Further, YOYO-1 exhibits characteristic absorption shifts upon binding to the Aβ(1–42) fibrils that we attribute to a self-stacking to non-stacking transition in its homodimer configuration; herein we show how this phenomenon can be exploited to estimate the degree of dye binding. Furthermore, we show that YOYO-1 can be used to monitor the kinetics of amyloid formation reactions. Taken together, our results show that YOYO-1 is a sensitive amyloid probe that can operate with both absorption and fluorescence read-outs, and this suggests that this commercially available dye could become a useful complement to thioflavin-T for in vitro amyloid-sensing applications.

Primary Nucleation Kinetics of Short Fibril-Forming Amyloidogenic Peptides.

The primary nucleation step in amyloid fibril formation can, depending on the nature of peptide sequence, occur in one step, straight from a dilute solution, or in multiple steps, via oligomers or disordered aggregates. The precise kinetic pathways of these processes are poorly understood. Employing forward flux sampling and a midresolution coarse-grained force field, we analyzed the reactive pathways from the solvated state to the fibril nucleus for a system of 12 amyloidogenic peptides. In line with previous work, increasing the overall side-chain hydrophobicity switches the fibrillization mechanism from one- to two-step nucleation. Overall, in this mechanism, peptides first form dimers and trimers, which then grow into a β-sheet. This sheet serves as a template for nucleation of additional β sheets until the fibril nucleus is fully formed. Our simulations indicate that the presence of the recently predicted polymerized phase in the nucleation pathway of intermediately hydrophobic peptides slows down the dynamics of fibril formation considerably, which may influence the time scale on which toxic early oligomers exist. The structure of the amyloid fibrils was found to be strongly dependent on the relative hydrophobic strength of side chains along the sequence: β sheets in the fibril are oriented such that a core of the relative strongest hydrophobic residues is formed along the fibril axis.

Peptide dimer structure in an Aβ(1–42) fibril visualized with cryo-EM

Alzheimer's disease (AD) is a fatal neurodegenerative disorder in humans and the main cause of dementia in aging societies. The disease is characterized by the aberrant formation of β-amyloid (Aβ) peptide oligomers and fibrils. These structures may damage the brain and give rise to cerebral amyloid angiopathy, neuronal dysfunction, and cellular toxicity. Although the connection between AD and Aβ fibrillation is extensively documented, much is still unknown about the formation of these Aβ aggregates and their structures at the molecular level. Here, we combined electron cryomicroscopy, 3D reconstruction, and integrative structural modeling methods to determine the molecular architecture of a fibril formed by Aβ(1-42), a particularly pathogenic variant of Aβ peptide. Our model reveals that the individual layers of the Aβ fibril are formed by peptide dimers with face-to-face packing. The two peptides forming the dimer possess identical tilde-shaped conformations and interact with each other by packing of their hydrophobic C-terminal β-strands. The peptide C termini are located close to the main fibril axis, where they produce a hydrophobic core and are surrounded by the structurally more flexible and charged segments of the peptide N termini. The observed molecular architecture is compatible with the general chemical properties of Aβ peptide and provides a structural basis for various biological observations that illuminate the molecular underpinnings of AD. Moreover, the structure provides direct evidence for a steric zipper within a fibril formed by full-length Aβ peptide.

Diagnostics of the acute coronary insufficiency by the method of Muller-matrix analysis of the optic anisotropy of myosin networks of the myocardium. A statistical and fractal approach.

Background. The acute coronary insufficiency is a common pathology in the practice of forensic experts. A small window of opportunity to study changes in myocardial tissue after death is a challenge for forensic experts. It is known that the established methods of detecting lesions of acute ischemia that are used in forensic practice need to be considerably updated since they depend on a multitude of internal and external environmental factors, require expensive reagents and are time consuming. These are precise reasons for searching and improving existing methods of diagnostics of myocardial changes to develop objective criteria for forensic determination of acute ischemic myocardial injury. Objective. To study the structure of the human myocardium under the acute coronary insufficiency using Mueller - matrix analysis of the optical anisotropy myosin networks of myocardium using a statistical and fractal approach. Methods. The study of myocardial samples was conducted with a laser polarimeter with subsequent analysis of the results in the MathLab 6 program. The object of the study was native myocardial sections of people who died as a result of acute coronary insufficiency and chronic ischemic heart disease. Results. We have revealed that in acute coronary insufficiency there was a decrease (20-fold) in the number of extreme values of the "orientational" Mueller matrix element of myocardial tissue. In other words, there is a clear disorientation of the optical axes of myosin fibrils in cases of acute coronary insufficiency comparing with chronic ischemic heart disease. Conclusion. We can assert the essential diagnostic sensitivity of laser polarimetry to differentiate death due to chronic ischemic heart disease and acute coronary insufficiency.

Nanoscale Swelling Heterogeneities in Type I Collagen Fibrils.

The distribution of water within the supramolecular structure of collagen fibrils is important for understanding their mechanical properties as well as the biomineralization processes in collagen-based tissues. We study the influence of water on the shape and the mechanical properties of reconstituted fibrils of type I collagen on the nanometer scale. Fibrils adsorbed on a silicon substrate were imaged with multiset point intermittent contact (MUSIC)-mode atomic force microscopy (AFM) in air at 28% relative humidity (RH) and in a hydrated state at 78% RH. Our data reveal the differences in the water uptake between the gap and overlap regions during swelling. This provides direct evidence for different amounts of bound and free water within the gap and overlap regions. In the dry state, the characteristic D-band pattern visible in AFM images is due to height corrugations along a fibril's axis. In the hydrated state, the fibril's surface is smooth and the D-band pattern reflects the different mechanical properties of the gap and overlap regions.

Predicting the aggregation propensity of prion sequences

The presence of prions can result in debilitating and neurodegenerative diseases in mammals and protein-based genetic elements in fungi. Prions are defined as a subclass of amyloids in which the self-aggregation process becomes self-perpetuating and infectious. Like all amyloids, prions polymerize into fibres with a common core formed of β-sheet structures oriented perpendicular to the fibril axes which form a structure known as a cross-β structure. The intermolecular β-sheet propensity, a characteristic of the amyloid pattern, as well as other key parameters of amyloid fibril formation can be predicted. Mathematical algorithms have been proposed to predict both amyloid and prion propensities. However, it has been shown that the presence of amyloid-prone regions in a polypeptide sequence could be insufficient for amyloid formation. It has also often been stated that the formation of amyloid fibrils does not imply that these are prions. Despite these limitations, in silico prediction of amyloid and prion propensities should help detect potential new prion sequences in mammals. In addition, the determination of amyloid-prone regions in prion sequences could be very useful in understanding the effect of sporadic mutations and polymorphisms as well as in the search for therapeutic targets.

Tunable assembly of amyloid-forming peptides into nanosheets as a retrovirus carrier

Using and engineering amyloid as nanomaterials are blossoming trends in bionanotechnology. Here, we show our discovery of an amyloid structure, termed "amyloid-like nanosheet," formed by a key amyloid-forming segment of Alzheimer's Aβ. Combining multiple biophysical and computational approaches, we proposed a structural model for the nanosheet that is formed by stacking the amyloid fibril spines perpendicular to the fibril axis. We further used the nanosheet for laboratorial retroviral transduction enhancement and directly visualized the presence of virus on the nanosheet surface by electron microscopy. Furthermore, based on our structural model, we designed nanosheet-forming peptides with different functionalities, elucidating the potential of rational design for amyloid-based materials with novel architecture and function.

Contributions of Raman spectroscopy to the understanding of bone strength.

Raman spectroscopy is increasingly commonly used to understand how changes in bone composition and structure influence tissue-level bone mechanical properties. The spectroscopic technique provides information on bone mineral and matrix collagen components and on the effects of various matrix proteins on bone material properties as well. The Raman spectrum of bone not only contains information on bone mineral crystallinity that is related to bone hardness but also provides information on the orientation of mineral crystallites with respect to the collagen fibril axis. Indirect information on collagen cross-links is also available and will be discussed. After a short introduction to bone Raman spectroscopic parameters and collection methodologies, advances in in vivo Raman spectroscopic measurements for animal and human subject studies will be reviewed. A discussion on the effects of aging, osteogenesis imperfecta, osteoporosis and therapeutic agents on bone composition and mechanical properties will be highlighted, including genetic mouse models in which structure-function and exercise effects are explored. Similarly, extracellular matrix proteins, proteases and transcriptional proteins implicated in the regulation of bone material properties will be reviewed.

Mechanisms of amyloid fibril formation.

Amyloid and amyloid-like aggregates are elongated unbranched fibrils consisting of β-structures of separate monomers positioned perpendicular to the fibril axis and stacked strictly above each other. In their physicochemical properties, amyloid fibrils are reminiscent of synthetic polymers rather than usual proteins because they are stable to the action of denaturing agents and proteases. Their mechanical stability can be compared to a spider's web, that in spite of its ability to stretch, is stronger than steel. It is not surprising that a large number of diseases are accompanied with amyloid fibril depositing in different organs. Pathologies provoked by depositing of incorrectly folded proteins include Alzheimer's, Parkinson's, and Huntington's diseases. In addition, this group of diseases involves mucoviscidosis, some types of diabetes, and hereditary cataracts. Each type of amyloidosis is characterized by aggregation of a certain type of protein that is soluble in general, and thus leads to specific distortions of functions of the corresponding organs. Therefore, it is important to understand the process of transformation of "native" proteins to amyloid fibrils to clarify how these molecules acquire such strength and what key elements of this process determine the pathway of erroneous protein folding. This review presents our analysis of complied information on the mechanisms of formation and biochemical properties of amyloid fibrils.