3D Lattice Structure Control of Ordered Macroporous Material by Self-Assembly of Liquid Droplets

ABSTRACTAggregates of the RNA binding protein TDP-43 are a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which are neurodegenerative disorders with overlapping clinical, genetic and pathological features. Mutations in the TDP-43 gene are causative of ALS, supporting its central role in pathogenesis. The process of TDP-43 aggregation remains poorly understood and whether this includes formation of intermediate complexes is unknown. We characterized aggregates derived from purified TDP-43 as a function of time and analyzed them under semi-denaturing conditions. Our assays identified oligomeric complexes at the initial time points prior to the formation of large aggregates, suggesting that ordered oligomerization is an intermediate step of TDP-43 aggregation. In addition, we analyzed liquid-liquid phase separation of TDP-43 and detected similar oligomeric assembly upon the maturation of liquid droplets into solid-like fibrils. These results strongly suggest that the oligomers form during the early steps of TDP-43 misfolding. Importantly, ALS-linked mutations A315T and M337V significantly accelerate aggregation, rapidly decreasing the monomeric population and shortening the oligomeric phase. We also show that the aggregates generated from purified protein seed intracellular aggregation, which is detected by established markers of TDP-43 pathology. Remarkably, cytoplasmic aggregate propagation is detected earlier with A315T and M337V and is 50% more widespread than with wild-type aggregates. Our findings provide evidence for a controlled process of TDP-43 self-assembly into intermediate structures that provide a scaffold for aggregation. This process is altered by ALS-linked mutations, underscoring the role of perturbations in TDP-43 homeostasis in protein aggregation and ALS-FTD pathogenesis.

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Segmentation in cohesive systems constrained by elastic environments

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2016.0160 ◽

2017 ◽

Vol 375 (2093) ◽

pp. 20160160 ◽

Cited By ~ 6

Author(s):

I. Novak ◽

L. Truskinovsky

Keyword(s):

Self Assembly ◽

Lattice Structure ◽

Media Theory ◽

Biological Applications ◽

Competing Interactions ◽

Complete Set ◽

Mass Spring ◽

Peculiar Nature ◽

The Continuum

The complexity of fracture-induced segmentation in elastically constrained cohesive (fragile) systems originates from the presence of competing interactions. The role of discreteness in such phenomena is of interest in a variety of fields, from hierarchical self-assembly to developmental morphogenesis. In this paper, we study the analytically solvable example of segmentation in a breakable mass–spring chain elastically linked to a deformable lattice structure. We explicitly construct the complete set of local minima of the energy in this prototypical problem and identify among them the states corresponding to the global energy minima. We show that, even in the continuum limit, the dependence of the segmentation topology on the stretching/pre-stress parameter in this problem takes the form of a devil's type staircase. The peculiar nature of this staircase, characterized by locking in rational microstructures, is of particular importance for biological applications, where its structure may serve as an explanation of the robustness of stress-driven segmentation. This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’

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1D Roughness Driven Depinning of Self-Assembly of Liquid Droplets

Langmuir ◽

10.1021/acs.langmuir.9b02600 ◽

2019 ◽

Vol 35 (45) ◽

pp. 14576-14585

Author(s):

K. Nilavarasi ◽

Ramkumar S. G. ◽

V. Madhurima

Keyword(s):

Self Assembly ◽

Liquid Droplets

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Self-Assembly of Porous Structures From a Binary Mixture of Lobed Patchy Particles

Frontiers in Physics ◽

10.3389/fphy.2021.767623 ◽

2021 ◽

Vol 9 ◽

Author(s):

Sanjib Paul ◽

Harish Vashisth

Keyword(s):

Binary Mixture ◽

Self Assembly ◽

The Self ◽

Amorphous Wire ◽

Liquid Droplets ◽

Jones Potential ◽

Patchy Particles ◽

Heterogeneous Structures ◽

Ring Structures ◽

Self Assembled

We report simulation studies on the self-assembly of a binary mixture of snowman and dumbbell shaped lobed particles. Depending on the lobe size and temperature, different types of self-assembled structures (random aggregates, spherical aggregates, liquid droplets, amorphous wire-like structures, amorphous ring structures, crystalline structures) are observed. At lower temperatures, heterogeneous structures are formed for lobed particles of both shapes. At higher temperatures, homogeneous self-assembled structures are formed mainly by the dumbbell shaped particles, while the snowman shaped particles remain in a dissociated state. We also investigated the porosities of self-assembled structures. The pore diameters in self-assemblies increased with an increase in temperature for a given lobe size. The particles having smaller lobes produced structures with larger pores than the particles having larger lobes. We further investigated the effect of σ, a parameter in the surface-shifted Lennard-Jones potential, on the self-assembled morphologies and their porosities. The self-assembled structures formed at a higher σ value are found to produce larger pores than those at a lower σ.

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Phase Separation of Shell Protein and Enzyme: An Insight into the Biogenesis of a Prokaryotic Metabolosome

10.1101/2022.01.14.476392 ◽

2022 ◽

Author(s):

Gaurav Kumar ◽

Sharmistha Sinha

Keyword(s):

Phase Separation ◽

Protein Interactions ◽

Self Assembly ◽

Bacterial Species ◽

Protein Structures ◽

The Self ◽

Liquid Droplets ◽

Shell Protein ◽

Shell Proteins

Bacterial microcompartments are substrate specific metabolic modules that are conditionally expressed in certain bacterial species. These all protein structures have size in the range of 100-150 nm and are formed by the self-assembly of thousands of protein subunits, all encoded by genes belonging to a single operon. The operon contains genes that encode for both enzymes and shell proteins. The shell proteins self-assemble to form the outer coat of the compartment and enzymes are encapsulated within. A perplexing question in MCP biology is to understand the mechanism which governs the formation of these small yet complex assemblages of proteins. In this work we use 1,2-propanediol utilization microcompartments (PduMCP) as a paradigm to identify the factors that drive the self-assembly of MCP proteins. We find that a major shell protein PduBB tend to self-assemble under macromolecular crowded environment and suitable ionic strength. Microscopic visualization and biophysical studies reveal phase separation to be the principle mechanism behind the self-association of shell protein in the presence of salts and macromolecular crowding. The shell protein PduBB interacts with the enzyme diol-dehydratase PduCDE and co-assemble into phase separated liquid droplets. The co-assembly of PduCDE and PduBB results in the enhancement of catalytic activity of the enzyme. A combination of spectroscopic and biochemical techniques shows the relevance of divalent cation Mg2+ in providing stability to intact PduMCP in vivo. Together our results suggest a combination of protein-protein interactions and phase separation guiding the self-assembly of Pdu shell protein and enzyme in solution phase.

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How faceted liquid droplets grow tails

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1515614113 ◽

2016 ◽

Vol 113 (3) ◽

pp. 493-496 ◽

Cited By ~ 41

Author(s):

Shani Guttman ◽

Zvi Sapir ◽

Moty Schultz ◽

Alexander V. Butenko ◽

Benjamin M. Ocko ◽

...

Keyword(s):

Melting Point ◽

Interfacial Tension ◽

Everyday Life ◽

Self Assembly ◽

Liquid Droplets ◽

Scale Elasticity ◽

Dispersed Oil ◽

Molecular Scale ◽

Future Technologies ◽

Shape Changes

Liquid droplets, widely encountered in everyday life, have no flat facets. Here we show that water-dispersed oil droplets can be reversibly temperature-tuned to icosahedral and other faceted shapes, hitherto unreported for liquid droplets. These shape changes are shown to originate in the interplay between interfacial tension and the elasticity of the droplet’s 2-nm-thick interfacial monolayer, which crystallizes at some T = Ts above the oil’s melting point, with the droplet’s bulk remaining liquid. Strikingly, at still-lower temperatures, this interfacial freezing (IF) effect also causes droplets to deform, split, and grow tails. Our findings provide deep insights into molecular-scale elasticity and allow formation of emulsions of tunable stability for directed self-assembly of complex-shaped particles and other future technologies.

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Structure control of nanoparticle superstructures with DNA nanostructure

Impact ◽

10.21820/23987073.2018.3.72 ◽

2018 ◽

Vol 2018 (3) ◽

pp. 72-73

Author(s):

Miho Tagawa ◽

Takumi Isogai ◽

Hayato Sumi ◽

Shoko Kojima

Keyword(s):

Self Assembly ◽

New Technology ◽

Natural World ◽

Neural Computing ◽

Binding Agent ◽

Buffer Solution ◽

Structure Control ◽

Dna Nanostructure ◽

Stable Clusters ◽

And Control

Nanoparticles are tiny stable clusters of atoms or molecules of between one and 100 nanometres. In comparison, the width of a human hair ranges from 80,000 to 100,000 nanometres. At this scale, particles sometimes exhibit unexpected properties, and structured assemblies of nanoparticles can have characteristics which are not found in the natural world. These varied and novel properties are finding applications in new technology domains such as nano-optics, neural computing, nanoscale transistors and cloaking devices. A research group at Nagoya University, led by Professor Miho Tagawa and including Dr Takumi Isogai, graduate students Hayato Sumi and Shoko Kojima, is working at the cutting edge of nanotechnology, finding ways to programme and control the structure of nanoparticle crystals and lattices using DNA mediation. As Tagawa says: 'programmable self-assembly of matter represents a big challenge in the field of material science and nanotechnology. It will lay the foundations for the creation of highly novel materials and devices, based on the specific properties of nanoparticles.' The project is funded by a range of Japanese agencies, including government ministries and private foundations. Nanoparticle crystals Nanoparticle crystallisation is difficult because of the various molecular interactions within and between particles and with the solvent. In 2008, it was discovered that using strands of DNA as surface ligands on nanoparticles would cause nanoparticles to assemble in crystalline structures similar to those exhibited by atoms. The surface strands of DNA interlink through hybridisation and act as a binding agent between the nanoparticles. Varying the lengths and segment types causes the particles to bind in different ways and thus exhibit different properties. Much has been learned about DNA-nanoparticle (DNA-NP). However, many challenges remain. Tagawa elaborates: 'whereas crystals of DNA-NP superlattice are stable when in a buffer solution, they tend to lose their symmetry when dried and exposed to air.' The team at Nagoya were determined to find a means of stabilising these structures after dehydration.

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Enhancing antibacterial activity of geminized cationic amphiphilic polymer via structure control and self-assembly regulation

Journal of Industrial and Engineering Chemistry ◽

10.1016/j.jiec.2020.07.038 ◽

2020 ◽

Vol 90 ◽

pp. 371-378 ◽

Cited By ~ 1

Author(s):

Ting Chen ◽

Lianyu Zhao ◽

Ziyuan Wang ◽

Jishi Zhao ◽

Yan Li ◽

...

Keyword(s):

Antibacterial Activity ◽

Self Assembly ◽

Amphiphilic Polymer ◽

Structure Control

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RNA sequence and structure control assembly and function of RNA condensates

RNA ◽

10.1261/rna.078875.121 ◽

2021 ◽

Vol 27 (12) ◽

pp. 1589-1601

Author(s):

Raghav R. Poudyal ◽

Jacob P. Sieg ◽

Bede Portz ◽

Christine D. Keating ◽

Philip C. Bevilacqua

Keyword(s):

Self Assembly ◽

Rna Structure ◽

Rna Stability ◽

Protein Biochemistry ◽

Structure Control ◽

Sequence Elements ◽

Control Assembly ◽

And Function ◽

Insight Into ◽

Liquid Liquid Phase Separation

Intracellular condensates formed through liquid–liquid phase separation (LLPS) primarily contain proteins and RNA. Recent evidence points to major contributions of RNA self-assembly in the formation of intracellular condensates. As the majority of previous studies on LLPS have focused on protein biochemistry, effects of biological RNAs on LLPS remain largely unexplored. In this study, we investigate the effects of crowding, metal ions, and RNA structure on formation of RNA condensates lacking proteins. Using bacterial riboswitches as a model system, we first demonstrate that LLPS of RNA is promoted by molecular crowding, as evidenced by formation of RNA droplets in the presence of polyethylene glycol (PEG 8K). Crowders are not essential for LLPS, however. Elevated Mg2+ concentrations promote LLPS of specific riboswitches without PEG. Calculations identify key RNA structural and sequence elements that potentiate the formation of PEG-free condensates; these calculations are corroborated by key wet-bench experiments. Based on this, we implement structure-guided design to generate condensates with novel functions including ligand binding. Finally, we show that RNA condensates help protect their RNA components from degradation by nucleases, suggesting potential biological roles for such higher-order RNA assemblies in controlling gene expression through RNA stability. By utilizing both natural and artificial RNAs, our study provides mechanistic insight into the contributions of intrinsic RNA properties and extrinsic environmental conditions to the formation and regulation of condensates comprised of RNAs.

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