Developing A Programmable, Self-Assembling Squash Leaf Curl China Virus (SLCCNV) Capsid Proteins Into “Nano-Cargo”-Like Architecture: A Next-Generation “Nanotool” For Biomedical Applications

AbstractA new era has begun in which pathogens have become useful scaffolds for nanotechnology applications. In this research/study, an attempt has been made to generate an empty cargo-like architecture from a high-profile plant pathogen of Squash leaf curl China virus (SLCCNV). In this approach, SLCCNV coat protein monomers are obtained efficiently by using a yeast Pichia pastoris expression system. Further, dialysis of purified SLCCNV-CP monomers against various pH strengthenened (5–10) disassembly and assembly buffers produced a self-assembled “Nanocargo”-like architecture, which also exhibited an ability to encapsulate the magnetic nanoparticles at in vitro. Bioinformatics tools were also utilized to predict the possible self-assembly kinetics and bioconjugation sites as well. The biocompatibility of “SLCNNV-CP-Nanocargo” particles was also evaluated by in vitro cancer cells, which eventually proved the particles to be versatile material for the next generation “nanotool” capable of housing various therapeutic or imaging agents.

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A New Hope: Self-Assembling Peptides with Antimicrobial Activity

Pharmaceutics ◽

10.3390/pharmaceutics11040166 ◽

2019 ◽

Vol 11 (4) ◽

pp. 166 ◽

Cited By ~ 24

Author(s):

Lucia Lombardi ◽

Annarita Falanga ◽

Valentina Del Genio ◽

Stefania Galdiero

Keyword(s):

Self Assembly ◽

Biomedical Applications ◽

High Specificity ◽

Antibacterial Activities ◽

Mechanisms Of Action ◽

Great Promise ◽

Functional Nanomaterials ◽

Self Assembling ◽

Low Toxicity ◽

Bio Compatibility

Peptide drugs hold great promise for the treatment of infectious diseases thanks to their novel mechanisms of action, low toxicity, high specificity, and ease of synthesis and modification. Naturally developing self-assembly in nature has inspired remarkable interest in self-assembly of peptides to functional nanomaterials. As a matter of fact, their structural, mechanical, and functional advantages, plus their high bio-compatibility and bio-degradability make them excellent candidates for facilitating biomedical applications. This review focuses on the self-assembly of peptides for the fabrication of antibacterial nanomaterials holding great interest for substituting antibiotics, with emphasis on strategies to achieve nano-architectures of self-assembly. The antibacterial activities achieved by these nanomaterials are also described.

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Self Assembling Nanostructured Delivery Vehicles for Biochemically Reactive Pairs

MRS Proceedings ◽

10.1557/proc-351-109 ◽

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.

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On the Aqueous Solution Behavior of C-Substituted 3,1,2-Ruthenadicarbadodecaboranes

Inorganics ◽

10.3390/inorganics7070091 ◽

2019 ◽

Vol 7 (7) ◽

pp. 91 ◽

Cited By ~ 3

Author(s):

Marta Gozzi ◽

Benedikt Schwarze ◽

Peter Coburger ◽

Evamarie Hey-Hawkins

Keyword(s):

Aqueous Solution ◽

Aqueous Solutions ◽

Self Assembly ◽

Self Assembling ◽

Vis Spectroscopy ◽

Assembly Behavior ◽

Biological Performance ◽

Type 3

3,1,2-Ruthenadicarbadodecaborane complexes bearing the [C2B9H11]2− (dicarbollide) ligand are robust scaffolds, with exceptional thermal and chemical stability. Our previous work has shown that these complexes possess promising anti-tumor activities in vitro, and tend to form aggregates (or self-assemblies) in aqueous solutions. Here, we report on the synthesis and characterization of four ruthenium(II) complexes of the type [3-(η6-arene)-1,2-R2-3,1,2-RuC2B9H9], bearing either non-polar (R = Me (2–4)) or polar (R = CO2Me (7)) substituents at the cluster carbon atoms. The behavior in aqueous solution of complexes 2, 7 and the parent unsubstituted [3-(η6-p-cymene)-3,1,2-RuC2B9H11] (8) was investigated via UV-Vis spectroscopy, mass spectrometry and nanoparticle tracking analysis (NTA). All complexes showed spontaneous formation of self-assemblies (108–109 particles mL−1), at low micromolar concentration, with high polydispersity. For perspective applications in medicine, there is thus a strong need for further characterization of the spontaneous self-assembly behavior in aqueous solutions for the class of neutral metallacarboranes, with the ultimate scope of finding the optimal conditions for exploiting this self-assembling behavior for improved biological performance.

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Virus assembly occurs following a pH- or Ca 2+ -triggered switch in the thermodynamic attraction between structural protein capsomeres

Journal of The Royal Society Interface ◽

10.1098/rsif.2009.0175 ◽

2009 ◽

Vol 7 (44) ◽

pp. 409-421 ◽

Cited By ~ 34

Author(s):

Yap P. Chuan ◽

Yuan Y. Fan ◽

Linda H. L. Lua ◽

Anton P. J. Middelberg

Keyword(s):

Self Assembly ◽

Virus Assembly ◽

Chemical Change ◽

Second Virial Coefficient ◽

Direct Proof ◽

Viral Assembly ◽

Structural Protein ◽

Salting Out ◽

Self Assembling

Viral self-assembly is of tremendous virological and biomedical importance. Although theoretical and crystallographic considerations suggest that controlled conformational change is a fundamental regulatory mechanism in viral assembly, direct proof that switching alters the thermodynamic attraction of self-assembling components has not been provided. Using the VP1 protein of polyomavirus, we report a new method to quantitatively measure molecular interactions under conditions of rapid protein self-assembly. We show, for the first time, that triggering virus capsid assembly through biologically relevant changes in Ca 2+ concentration, or pH, is associated with a dramatic increase in the strength of protein molecular attraction as quantified by the second virial coefficient ( B 22 ). B 22 decreases from −2.3 × 10 −4 mol ml g −2 (weak protein–protein attraction) to −2.4 × 10 −3 mol ml g −2 (strong protein attraction) for metastable and Ca 2+ -triggered self-assembling capsomeres, respectively. An assembly-deficient mutant (VP1CΔ63) is conversely characterized by weak protein–protein repulsion independently of chemical change sufficient to cause VP1 assembly. Concomitant switching of both VP1 assembly and thermodynamic attraction was also achieved by in vitro changes in ammonium sulphate concentration, consistent with protein salting-out behaviour. The methods and findings reported here provide new insight into viral assembly, potentially facilitating the development of new antivirals and vaccines, and will open the way to a more fundamental physico-chemical description of complex protein self-assembly systems.

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Evolving Reaction-Diffusion Ecosystems with Self-Assembling Structures in Thin Films

Artificial Life ◽

10.1162/106454698568422 ◽

1998 ◽

Vol 4 (1) ◽

pp. 25-40 ◽

Cited By ~ 27

Author(s):

Jens Breyer ◽

Jörg Ackermann ◽

John McCaskill

Keyword(s):

Self Assembly ◽

Flexible Structures ◽

Reaction Diffusion ◽

In Vitro Evolution ◽

Spatially Resolved ◽

Self Assembling ◽

Artificial Dna ◽

Additional Stabilization ◽

Artificial Chemistries

Recently, new types of coupled isothermal polynucleotide amplification reactions for the investigation of in vitro evolution have been established that are based on the multi-enzyme 3SR reaction. Microstructured thin-film open bioreactors have been constructed in our laboratory to run these reactions spatially resolved in flow experiments. Artificial DNA/RNA chemistries close to the in vitro biochemistry of these systems have been developed, which we have studied in computer simulations in configurable hardware (NGEN). These artificial chemistries are described on the level of individual polynucleotide molecules, each with a defined sequence, and their complexes. The key feature of spatial pattern formation provides a weak stabilization of cooperative catalytic properties of the evolving molecules. Of great interest is the step to include extended self-assembly processes of flexible structures—allowing the additional stabilization of cooperation through semipermeable, flexible, self-organizing membrane boundaries. We show how programmable matter simulations of experimentally relevant molecular in vitro evolution can be extended to include the influence of self-assembling flexible membranes.

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Monitoring the Early Stage Self-Assembly of Enzyme-Assisted Peptide Hydrogels

Australian Journal of Chemistry ◽

10.1071/ch12557 ◽

2013 ◽

Vol 66 (5) ◽

pp. 572 ◽

Cited By ~ 9

Author(s):

Richard J. Williams ◽

James Gardiner ◽

Anders B. Sorensen ◽

Silvia Marchesan ◽

Roger J. Mulder ◽

...

Keyword(s):

1H Nmr ◽

Self Assembly ◽

Early Stage ◽

The Self ◽

Spectroscopic Techniques ◽

Subsequent Formation ◽

Self Assembling ◽

Hydrogel Formation ◽

Assembly Kinetics ◽

Peptide Hydrogels

The early stages of the self-assembly of peptide hydrogels largely determine their final material properties. Here we discuss experimental methodologies for monitoring the self-assembly kinetics which underpin peptide hydrogel formation. The early stage assembly of an enzyme-catalysed Fmoc-trileucine based self-assembled hydrogel was examined using spectroscopic techniques (circular dichroism, CD, and solution NMR) as well as chromatographic (HPLC) and mechanical (rheology) techniques. Optimal conditions for enzyme-assisted hydrogel formation were identified and the kinetics examined. A lag time associated with the formation and accumulation of the self-assembling peptide monomer was observed and a minimum hydrogelator concentration required for gelation was identified. Subsequent formation of well defined nano- and microscale structures lead to self-supporting hydrogels at a range of substrate and enzyme concentrations. 1H NMR monitoring of the early self-assembly process revealed trends that were well in agreement with those identified using traditional methods (i.e. HPLC, CD, rheology) demonstrating 1H NMR spectroscopy can be used to non-invasively monitor the self-assembly of peptide hydrogels without damaging or perturbing the system.

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Lipid membranes trigger misfolding and self-assembly of amyloid β 42 protein into aggregates

10.1101/587493 ◽

2019 ◽

Author(s):

Siddhartha Banerjee ◽

Mohtadin Hashemi ◽

Karen Zagorski ◽

Yuri L. Lyubchenko

Keyword(s):

Self Assembly ◽

Lipid Membranes ◽

Membrane Surface ◽

Amyloid Β ◽

Test Tube ◽

Aggregation Process ◽

Self Assembling ◽

Nanoscale Aggregates

AbstractThe assembly of polypeptides and proteins into nanoscale aggregates is a phenomenon observed in a vast majority of proteins. Importantly, aggregation of amyloid β (Aβ) proteins is considered as a major cause for the development of Alzheimer’s disease. The process depends on various conditions and typical test-tube experiments require high protein concentration that complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here we demonstrate that Aβ42 monomers at the membrane bilayer are capable of self-assembling into aggregates at physiologically low concentrations, and the membrane in this aggregation process plays a role of a catalyst. We applied all-atom molecular dynamics to demonstrate that the interaction with the membrane surface dramatically changes the conformation of Aβ42 protein. As a result, the misfolded Aβ42 rapidly assembles into dimers, trimers and tetramers, so the on-surface aggregation is the mechanism by which amyloid oligomers are produced and spread.

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Temperature-dependent Self assembly of biofilaments during red blood cell sickling

10.1101/2021.03.07.433773 ◽

2021 ◽

Author(s):

Arabinda Behera ◽

Oshin Sharma ◽

Debjani Paul ◽

Anirban Sain

Keyword(s):

Self Assembly ◽

Kinetic Monte Carlo ◽

Lag Time ◽

Vital Role ◽

Temperature Dependent ◽

Opposite Case ◽

Assembly Kinetics ◽

The Mean ◽

Kinetics Of

Molecular self-assembly plays vital role in various biological functions. However, when aberrant molecules self-assemble to form large aggregates, it can give rise to various diseases. For example, the sickle cell disease and Alzheimer’s disease are caused by self-assembled hemoglobin fibers and amyloid plaques, respectively. Here we study the assembly kinetics of such fibers using kinetic Monte-Carlo simulation. We focus on the initial lag time of these highly stochastic processes, during which self-assembly is very slow. The lag time distributions turn out to be similar for two very different regimes of polymerization, namely, a) when polymerization is slow and depolymerization is fast, and b) the opposite case, when polymerization is fast and depolymerization is slow. Using temperature dependent on- and off-rates for hemoglobin fiber growth, reported in recent in-vitro experiments, we show that the mean lag time can exhibit non-monotonic behaviour with respect to change of temperature.

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Norbornene-Functionalised Chitosan Hydrogels and Microgels via an Unprecedented Photo-Initiated Self-Assembly for Potential Biomedical Applications

10.26434/chemrxiv.12340484 ◽

2020 ◽

Author(s):

Sarah michel ◽

Alice Kilner ◽

Jean-Charles Eloi ◽

Sarah E rogers ◽

Wuge H. Briscoe ◽

...

Keyword(s):

Drug Delivery ◽

Self Assembly ◽

Biomedical Applications ◽

Hydrophobic Interactions ◽

Gelation Mechanism ◽

Swelling Behaviour ◽

Assembly Mechanism ◽

Significant Toxicity ◽

Chitosan Hydrogels

Access to biocompatible self-assembled gels and microgels is of great interests for a variety of biological applications from tissue engineering to drug delivery. Here, the facile synthesis of supramolecular hydrogels of norbornene (nb)-functionalised chitosan (CS-nb) via UV-triggered self-assembly in the presence of Irgacure 2959 (IRG) is reported. The in vitro stable hydrogels are injectable and showed pH-responsive swelling behaviour, while their structure and mechanical properties could be tuned by tailoring the stereochemistry of the norbornene derivative (e.g. endo- or -exo). Interestingly, unlike other nb-type hydrogels, the gels possess nanopores within their structure, which might lead to potential drug delivery applications. A gelation mechanism was proposed based on hydrophobic interactions following the combination of IRG on norbornene, as supported by 1H NMR. This self-assembly mechanism was used to access microgels of size 100-150 nm which could be further functionalised and showed no significant toxicity to human dermofibroblast cells.

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Controlling neuronal growth and connectivity via directed self-assembly of proteins

MRS Proceedings ◽

10.1557/opl.2013.338 ◽

2013 ◽

Vol 1498 ◽

pp. 207-212

Author(s):

Daniel Rizzo ◽

Ross Beighley ◽

James D. White ◽

Cristian Staii

Keyword(s):

Self Assembly ◽

Gold Surface ◽

Nerve Tissue ◽

3 Dimensional ◽

Force Microscopy ◽

Self Assembling ◽

Atomic Force ◽

Will Self ◽

Neuron Growth

ABSTRACTMaterials that offer the ability to influence tissue regeneration are of vital importance to the field of Tissue Engineering. Because valid 3-dimensional scaffolds for nerve tissue are still in development, advances with 2-dimensional surfaces in vitro are necessary to provide a complete understanding of controlling regeneration. Here we present a method for controlling nerve cell growth on Au electrodes using Atomic Force Microscopy -aided protein assembly. After coating a gold surface in a self-assembling monolayer of alkanethiols, the Atomic Force Microscope tip can be used to remove regions of the self-assembling monolayer in order to produce well-defined patterns. If this process is then followed by submersion of the sample into a solution containing neuro-compatible proteins, they will self assemble on these exposed regions of gold, creating well-specified regions for promoted neuron growth.

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