Amyloid Fibrils: From Disease to Design. New Biomaterial Applications for Self-Assembling Cross-β Fibrils

2007 ◽  
Vol 60 (5) ◽  
pp. 333 ◽  
Author(s):  
Sally L. Gras
Keyword(s):  
Enzyme Immobilization ◽  
Amyloid Fibrils ◽  
Protein Aggregates ◽  
Supporting Cells ◽  
Cell Behaviour ◽  
Biomimetic Materials ◽  
Self Assembling ◽  
Recent Advances ◽  
Positive Functions

Amyloid fibrils are self-assembling protein aggregates. They are essentially insoluble and resilient nanofibres that offer great potential as materials for nanotechnology and bionanotechnology. Fibrils are associated with several debilitating diseases, for example Alzheimer’s disease, but recent advances suggest they also have positive functions in nature and can be formed in vitro from generic proteins. This article explores how the unique nanotopography and advantageous properties of fibrils may be used to develop tools for probing cell behaviour, protein-based biomimetic materials for supporting cells, or platforms for biosensors and enzyme immobilization.

scholarly journals Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

2021 ◽  
Vol 9 ◽  
Author(s):  
Sepehr Shafiee ◽  
Siavash Shariatzadeh ◽  
Ali Zafari ◽  
Alireza Majd ◽  
Hassan Niknejad
Keyword(s):  
Biomechanical Properties ◽  
Supporting Cell ◽  
Culture Conditions ◽  
Vascular Network ◽  
Target Tissue ◽  
Supporting Cells ◽  
Recent Advances ◽  
Endothelial Lineage ◽  
Culture Strategies

Currently, the fabrication of a functional vascular network to maintain the viability of engineered tissues is a major bottleneck in the way of developing a more advanced engineered construct. Inspired by vasculogenesis during the embryonic period, the in vitro prevascularization strategies have focused on optimizing communications and interactions of cells, biomaterial and culture conditions to develop a capillary-like network to tackle the aforementioned issue. Many of these studies employ a combination of endothelial lineage cells and supporting cells such as mesenchymal stem cells, fibroblasts, and perivascular cells to create a lumenized endothelial network. These supporting cells are necessary for the stabilization of the newly developed endothelial network. Moreover, to optimize endothelial network development without impairing biomechanical properties of scaffolds or differentiation of target tissue cells, several other factors, including target tissue, endothelial cell origins, the choice of supporting cell, culture condition, incorporated pro-angiogenic factors, and choice of biomaterial must be taken into account. The prevascularization method can also influence the endothelial lineage cell/supporting cell co-culture system to vascularize the bioengineered constructs. This review aims to investigate the recent advances on standard cells used in in vitro prevascularization methods, their co-culture systems, and conditions in which they form an organized and functional vascular network.

Torus Circumference and Thickness Parameters From a Linear DNA Size Series Suggest How Toruses Self-Assemble

1985 ◽  
Vol 43 ◽  
pp. 522-523
Author(s):  
George C. Ruben ◽  
Kenneth A. Marx
Keyword(s):  
Tertiary Structure ◽  
Dna Complexes ◽  
Tertiary Structures ◽  
Self Assembling ◽  
Double Stranded Dna ◽  
Calf Thymus ◽  
Dna Organization ◽  
Condensed Dna ◽  
Dna Size

Certain double stranded DNA bacteriophage and viruses are thought to have their DNA organized into large torus shaped structures. Morphologically, these poorly understood biological DNA tertiary structures resemble spermidine-condensed DNA complexes formed in vitro in the total absence of other macromolecules normally synthesized by the pathogens for the purpose of their own DNA packaging. Therefore, we have studied the tertiary structure of these self-assembling torus shaped spermidine- DNA complexes in a series of reports. Using freeze-etch, low Pt-C metal (10-15Å) replicas, we have visualized the microscopic DNA organization of both calf Thymus( CT) and linear 0X-174 RFII DNA toruses. In these structures DNA is circumferentially wound, continuously, around the torus into a semi-crystalline, hexagonal packed array of parallel DNA helix sections.

scholarly journals Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiuye Li ◽  
W. Michael Babinchak ◽  
Witold K. Surewicz
Keyword(s):  
Amyloid Fibrils ◽  
Low Complexity ◽  
Structural Features ◽  
Protein Fragments ◽  
Hydrophobic Residues ◽  
Backbone Conformation ◽  
Hydrophobic Amino Acids ◽  
Insight Into ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of amyloid-like aggregates formed by the C-terminal fragments of TDP-43 that contain the low complexity domain of the protein. Here, we report the cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain in vitro at pH 4. This structure reveals single protofilament fibrils containing a large (139-residue), tightly packed core. While the C-terminal part of this core region is largely planar and characterized by a small proportion of hydrophobic amino acids, the N-terminal region contains numerous hydrophobic residues and has a non-planar backbone conformation, resulting in rugged surfaces of fibril ends. The structural features found in these fibrils differ from those previously found for fibrils generated from short protein fragments. The present atomic model for TDP-43 LCD fibrils provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.

scholarly journals Co-factor-free aggregation of tau into seeding-competent RNA-sequestering amyloid fibrils

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pijush Chakraborty ◽  
Gwladys Rivière ◽  
Shu Liu ◽  
Alain Ibáñez de Opakua ◽  
Rıza Dervişoğlu ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Corticobasal Degeneration ◽  
Binding Studies ◽  
Rigid Core ◽  
Tau Aggregation ◽  
The Brain ◽  
Tau Aggregate ◽  
Disease Specific ◽  
Tau Fibrils

AbstractPathological aggregation of the protein tau into insoluble aggregates is a hallmark of neurodegenerative diseases. The emergence of disease-specific tau aggregate structures termed tau strains, however, remains elusive. Here we show that full-length tau protein can be aggregated in the absence of co-factors into seeding-competent amyloid fibrils that sequester RNA. Using a combination of solid-state NMR spectroscopy and biochemical experiments we demonstrate that the co-factor-free amyloid fibrils of tau have a rigid core that is similar in size and location to the rigid core of tau fibrils purified from the brain of patients with corticobasal degeneration. In addition, we demonstrate that the N-terminal 30 residues of tau are immobilized during fibril formation, in agreement with the presence of an N-terminal epitope that is specifically detected by antibodies in pathological tau. Experiments in vitro and in biosensor cells further established that co-factor-free tau fibrils efficiently seed tau aggregation, while binding studies with different RNAs show that the co-factor-free tau fibrils strongly sequester RNA. Taken together the study provides a critical advance to reveal the molecular factors that guide aggregation towards disease-specific tau strains.

scholarly journals Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives

2021 ◽  
Vol 11 (5) ◽  
pp. 336
Author(s):  
Mohammed Ghiboub ◽  
Ahmed M. I. Elfiky ◽  
Menno P. J. de Winther ◽  
Nicola R. Harker ◽  
David F. Tough ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Inflammatory Diseases ◽  
Selective Inhibition ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Domain Specific ◽  
Recent Advances ◽  
Autoimmune And Inflammatory Diseases

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.

scholarly journals Newly Developed Self-Assembling Antioxidants as Potential Therapeutics for the Cancers

2021 ◽  
Vol 11 (2) ◽  
pp. 92 ◽  
Author(s):  
Babita Shashni ◽  
Yukio Nagasaki
Keyword(s):  
Cancer Survival ◽  
Self Assembling ◽  
Therapeutic Regime ◽  
Cancer Models ◽  
Secondary Messengers ◽  
Potential Therapeutics ◽  
Target Effects ◽  
Tempo Radical

Elevated reactive oxygen species (ROS) have been implicated as significant for cancer survival by functioning as oncogene activators and secondary messengers. Hence, the attenuation of ROS-signaling pathways in cancer by antioxidants seems a suitable therapeutic regime for targeting cancers. Low molecular weight (LMW) antioxidants such as 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO), although they are catalytically effective in vitro, exerts off-target effects in vivo due to their size, thus, limiting their clinical use. Here, we discuss the superior impacts of our TEMPO radical-conjugated self-assembling antioxidant nanoparticle (RNP) compared to the LMW counterpart in terms of pharmacokinetics, therapeutic effect, and adverse effects in various cancer models.

scholarly journals Formation of Amyloid Fibrils In Vitro from Partially Unfolded Intermediates of Human γC-Crystallin

2010 ◽  
Vol 51 (2) ◽  
pp. 672 ◽  
Author(s):  
Yongting Wang ◽  
Sarah Petty ◽  
Amy Trojanowski ◽  
Kelly Knee ◽  
Daniel Goulet ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Partially Unfolded

Self Assembling Nanostructured Delivery Vehicles for Biochemically Reactive Pairs

1994 ◽  
Vol 351 ◽  
Author(s):  
Nir Kossovsky ◽  
A. Gelman ◽  
H.J. Hnatyszyn ◽  
E. Sponsler ◽  
G.-M. Chow
Keyword(s):  
Physical Properties ◽  
Self Assembly ◽  
Materials Science ◽  
Technology Development ◽  
Biological Behavior ◽  
X Ray Diffraction ◽  
Self Assembling ◽  
Transmission Electron ◽  
Carbon Ceramic

ABSTRACTIntrigued by the deceptive simplicity and beauty of macromolecular self-assembly, our laboratory began studying models of self-assembly using solids, glasses, and colloidal substrates. These studies have defined a fundamental new colloidal material for supporting members of a biochemically reactive pair.The technology, a molecular transportation assembly, is based on preformed carbon ceramic nanoparticles and self assembled calcium-phosphate dihydrate particles to which glassy carbohydrates are then applied as a nanometer thick surface coating. This carbohydrate coated core functions as a dehydroprotectant and stabilizes surface immobilized members of a biochemically reactive pair. The final product, therefore, consists of three layers. The core is comprised of the ceramic, the second layer is the dehydroprotectant carbohydrate adhesive, and the surface layer is the biochemically reactive molecule for which delivery is desired.We have characterized many of the physical properties of this system and have evaluated the utility of this delivery technology in vitro and in animal models. Physical characterization has included standard and high resolution transmission electron microscopy, electron and x-ray diffraction and ζ potential analysis. Functional assays of the ability of the system to act as a nanoscale dehydroprotecting delivery vehicle have been performed on viral antigens, hemoglobin, and insulin. By all measures at present, the favorable physical properties and biological behavior of the molecular transportation assembly point to an exciting new interdisciplinary area of technology development in materials science, chemistry and biology.

Dynamics and Fluidity of Amyloid Fibrils:  A Model of Fibrous Protein Aggregates

2002 ◽  
Vol 124 (51) ◽  
pp. 15150-15151 ◽  
Author(s):  
Ami S. Lakdawala ◽  
David M. Morgan ◽  
Dennis C. Liotta ◽  
David G. Lynn ◽  
James P. Snyder
Keyword(s):  
Amyloid Fibrils ◽  
Protein Aggregates ◽  
Fibrous Protein
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