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Post by skyship on Feb 2, 2016 18:17:30 GMT -5
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Post by skyship on Feb 2, 2016 18:23:35 GMT -5
Compare filaments: Image: Look at enlarged image: pubs.acs.org/doi/full/10.1021/ma502264cFigure 1. A few illustrative examples of systems that can be analyzed by FiberApp software. (A) Bovine serum albumin (BSA) flexible (left) and rigid (right) amyloid fibrils.(63, 64) The inset images depict magnified areas of AFM images with point positioning along tracked contours with low and high intrinsic stiffness, respectively. (B) Simulated worm-like chain fibrils, generated directly in FiberApp software, providing a theoretical benchmark model against real systems.(66) (C) Functionalized multiwalled carbon nanotubes (the figure is adapted from Li et al.(67)). The inset image reflects the feasibility of tracking for hollow objects. (D) Circular DNA adsorbed on APTES-modified mica (with carrageenan fibrils in the background). Image courtesy of Larissa Schefer. (E) β-Lactoglobulin fibrils that form 2D liquid crystalline domains (left)(65) and circles (right), pointed by white arrows, at liquid interfaces (figure adapted from Jordens et al.(66)). (F) Wavy lysozyme amyloid fibrils with subpersistence-length complex scaling behavior (figure adapted from Lara et al.(69)). (G) Nanoclusters of Fe3O4 nanoparticles with β-lactoglobulin fibrils that can align in the presence of a magnetic field (figure adapted from Bolisetty et al.(70)). (H) Linear ι-carrageenan polysaccharide chains, prior (left) and after addition of salt (right), forming secondary structures and looped conformation.(57) Image courtesy of Larissa Schefer. The inset images demonstrate the possibility of closed-contour tracking. (I) TEMPO-oxidized wood cellulose nanofibrils with areas of different intrinsic stiffness (kinks), originating from the harsh mechanical treatment during sample preparation.(71) In the inset image it is demonstrated a concept of tracking with special masks that define contour segments with high curvature and low intrinsic stiffness.
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Post by skyship on Feb 2, 2016 18:25:23 GMT -5
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Post by skyship on Feb 2, 2016 18:28:01 GMT -5
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Post by skyship on Feb 2, 2016 18:29:38 GMT -5
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Post by skyship on Feb 2, 2016 18:33:19 GMT -5
Nanomechanics of functional and pathological amyloid materials Tuomas P. J. Knowles1 * and Markus J. Buehler2,3,4* Amyloid or amyloid-like fibrils represent a general class of nanomaterials that can be formed from many different peptides and proteins. Although these structures have an important role in neurodegenerative disorders, amyloid materials have also been exploited for functional purposes by organisms ranging from bacteria to mammals. Here we review the functional and pathological roles of amyloid materials and discuss how they can be linked back to their nanoscale origins in the structure and nanomechanics of these materials. We focus on insights both from experiments and simulations, and discuss how comparisons between functional protein filaments and structures that are assembled abnormally can shed light on the fundamental material selection criteria that lead to evolutionary bias in multiscale material design in nature. web.mit.edu/mbuehler/www/papers/Nature_Nanotechnology_2011.pdf
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Post by skyship on Feb 2, 2016 18:43:16 GMT -5
70. Bolisetty, S.; Vallooran, J. J.; Adamcik, J.; Mezzenga, R. ACS Nano 2013, 7, 6146– 6155 [ACS Full Text ACS Full Text], [PubMed], [CAS] 70. Magnetic-Responsive Hybrids of Fe3O4 Nanoparticles with β-Lactoglobulin Amyloid Fibrils and Nanoclusters Bolisetty, Sreenath; Vallooran, Jijo J.; Adamcik, Jozef; Mezzenga, Raffaele ACS Nano (2013), 7 (7), 6146-6155 CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society) The authors report on the synthesis and magnetic-responsive behavior of hybrids formed by dispersing neg. charged Fe oxide (Fe3O4) magnetic nanoparticles in pos. charged β-lactoglobulin protein solns. at acidic pH, followed by heating at high temps. Depending on the pH used, different hybrid aggregates can be obtained, such as nanoparticle-modified amyloid fibrils (pH 3) and spherical nanoclusters (pH 4.5). The authors study the effect of magnetic fields of varying strengths (0-5 T) on the alignment of these Fe3O4-modified amyloid fibrils and spherical nanoclusters using a combination of scattering, birefringence and microscopic techniques and a strong alignment of the hybrids upon increasing the intensity of the magnetic field, which the authors quantify via 2-dimensional and 3-dimensional order parameters were found. The authors also demonstrate the possibility of controlling magnetically the sol-gel behavior of these hybrids: addn. of (NaCl, 150 mM) to a soln. contg. nanoparticles modified with β-lactoglobulin amyloid fibrils (2% fibrils modified with 0.6% Fe3O4 nanoparticles) induces 1st the formation of a reversible gel, which can then be converted back to soln. upon application of a moderate magnetic field of 1.1 T. These hybrids offer a new appealing functional colloidal system in which the aggregation, orientational order and rheol. behavior can be efficiently controlled in a purely noninvasive way by external magnetic fields of weak intensity. pubs.acs.org/doi/abs/10.1021/nn401988m
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Post by skyship on Feb 3, 2016 17:17:00 GMT -5
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Post by skyship on Feb 4, 2016 13:08:11 GMT -5
The toxicity of an “artificial” amyloid is related to how it interacts with membranes However, amyloids are also used for normal cellular functions.2 This is the case in unicellular cells (in E. coli and S. cerevisiae) in which amyloid proteins allow the fixation of cells onto a glass surface and the formation of biofilms, but amyloid proteins may also form prions that can help the cells to survive in particular conditions.3-6 This is also the case in metazoans with Pmel17, which is involved in mammalian skin pigmentation.7 Also, several endocrine hormones appear to be stored in secretory granules in an amyloid-like state.8 Interestingly, both toxic and non-toxic amyloids share common or closely related oligomeric species. These oligomeric species are produced early during polymerization kinetics and are recognized by the same antibodies. These antibodies are directed against artificially made oligomers, synthesized by coupling an Aß peptide to the surface of colloidal gold beads via its C-terminus. ...... www.researchgate.net/profile/Karine_Berthelot/publication/47701128_The_toxicity_of_an_artificial_amyloid_is_related_to_how_it_interacts_with_membranes/links/0deec51e3d5fc823e5000000.pdf
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Post by skyship on Feb 4, 2016 13:11:46 GMT -5
Amyloid Oligomers and Protofibrils, but Not Filaments, Self-Replicate from Native Lysozyme There is increasing evidence that amyloid formation proceeds along two distinct assembly pathways involving either globular oligomers and protofibrils or rigid monomeric filaments. Oligomers, in particular, have been implicated as the dominant molecular species responsible for pathogenesis. Yet the molecular mechanisms regulating their self-assembly have remained elusive. Here we show that oligomers/protofibrils and monomeric filaments, formed along distinct assembly pathways, display critical differences in their ability to template amyloid growth at physiological vs denaturing temperatures. At physiological temperatures, amyloid filaments remained stable but could not seed growth of native monomers. In contrast, oligomers and protofibrils not only remained intact but were capable of self-replication using native monomers as the substrate. Kinetic data further suggested that this prion-like growth mode of oligomers/protofibrils involved two distinct activities operating orthogonal from each other: autocatalytic self-replication of oligomers from native monomers and nucleated polymerization of oligomers into protofibrils. The environmental changes to stability and templating competence of these different amyloid species in different environments are likely to be important for understanding the molecular mechanisms underlying both pathogenic and functional amyloid self-assembly. pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2014/jacsat.2014.136.issue-25/ja502529m/20150602/images/medium/ja-2014-02529m_0009.gifpubs.acs.org/doi/abs/10.1021/ja502529mFunctional for what purpose? s
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Post by skyship on Feb 4, 2016 13:23:20 GMT -5
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Post by skyship on Feb 4, 2016 13:38:04 GMT -5
From Pathology to Functionality: Useful Amyloid and Their Widespread Prevalence .......... However, all is not doom and gloom with regards to amyloid. There is a growing number of examples of Amyloid structures performing beneficial functions in nature as functional amyloid.5,12–17 In humans, the Pmel17 protein deposits as insoluble structures which help form melanosomes with covalently linked melanin.18 The Pmel17 protein is incredibly aggregation-prone, even aggregating within seconds in molar concentrations of the powerful chemical denaturant guanidinium chloride.18 However, this potentially devastating potential is kept in check by having Pmel17 attached to a membrane, from which it is released controllably through protease cleavage and subsequent dissociation. Amyloid is also found in silk moth oocytes and embryos,19 spider silks20 and fungi such as Aspergillus where they help hyphae penetrate the air-water interface interface.21 www.ncbi.nlm.nih.gov/pmc/articles/PMC3268958/....... The archetypal CsgA, which is the major component of the E. coli amyloid structure called curli,28 fibrillates to the same amyloid structure in vitro under a broad range of pH, temperature, concentration and ionic strength, according to fiber diffraction and Fourier Transform Infrared Spectroscopy (Dueholm MS and Otzen DE, unpublished observations). Note that unphysiological extremes of pH may still lead to different structures, as seen by recent solid state NMR studies of the fungal HET-s protein at pH 3 versus pH 7 29. This evolutionarily optimized robustness of design means that amyloid can be used as reliable building material in materials ranging from the cement of barnacle adhesive plaques30 to templates for gold nanowires31 and biomimetic silks in materials and medical applications.32 The amyloid state has also been shown to constitute a storage state for peptide hormones normally secreted in secretory granules of the endocrine system,33 though in this case extreme stability is not desired; rather, the amyloid here has to constitute a rapidly mobilizable source of material and therefore the amyloid can probably dissociate quite simply by a switch in pH"......... "......Interestingly, functional amyloid may possess a unique structural fold rather than simply being the conventional cross-β structure observed in pathological amyloid by the combined efforts of fiber diffraction1,34 and X-ray crystallography.35,36 Although CsgA fibrils give rise to the classical diffraction distances at 5 and 10 Å characteristic of cross-β structures and representing inter-strand and inter-sheet distances, respectively, solid state NMR and electron microscopy fail to demonstrate the expected in-register parallel β-sheet architecture.37 It is speculated that CsgA may instead form β-helix structures.37 This is consistent with the reported β-solenoid structure of the fungal HET-s protein38 and our own observations that Pseudomonas amyloid gives rise to an additional diffraction distance around 6.3 Å, in addition to those corresponding to inter-strand and inter-sheet distances.27 It is worth noting that similar β-helix structures have been proposed for the passenger domains of bacterial autotransporters such as Ag43,39 which we have shown to generate Thioflavin-T positive structures in vivo.40 Future high-resolution structures of functional amyloid may resolve whether this unusual structure is formed in and contributes to the high stability of functional amyloid..... ......Conclusion Functional amyloid provides a fascinating new angle on the conundrum of why proteins have such a pronounced tendency to aggregate. Rather than being a malicious ploy to frustrate the protein scientist, this can actually serve a purpose or rather many different purposes. As a simple comparison between amyloid-producing operons from E. coli and Pseudomonas indicates, amyloid protein can be produced in many different ways and using different motifs. In teasing out the details of how nature manages to control and harness this potentially chaotic process to produce the grand architecture of cellular amyloid extensions by a suite of wonderfully adapted chaperone proteins, one is invariably reminded of the homage to a Greco-Egyptian queen that could just as well be penned to functional amyloid: Age cannot wither them nor custom stale their infinite variety".…......
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