Conformational Entropy Research Articles

MARTINI Coarse-Grained Force Field for Thermoplastic Starch Nanocomposites.

Thermoplastic starch (TPS) is an excellent film-forming material, and the addition of fillers, such as tetramethylammonium-montmorillonite (TMA-MMT) clay, has significantly expanded its use in packaging applications. We first used an all-atom (AA) simulation to predict several macroscopic (Young's modulus, glass transition temperature, density) and microscopic (conformation along 1-4 and 1-6 glycosidic linkages, composite morphology) properties of TPS melt and TPS-TMA-MMT composite. The interplay of polymer-surface (weakly repulsive), plasticizer-surface (attractive), and polymer-plasticizer (weakly attractive) interactions leads to conformational and dynamics properties distinct from those in systems with either attractive or repulsive polymer-surface interactions. A subset of AA properties was used to parametrize the MARTINI-2 coarse-grained (CG) force field (FF) for the melt and composite systems. The missing bonded parameters of amylose and amylopectin and the bead types for 1-4 and 1-6 linked α-D glucose were determined using two-body excess entropy, density, and bond and angle distributions in the AA TPS melt. This new MARTINI-2 CG model was also compared with the MARTINI-3 model for the TPS melt. However, the requirement of a polarizable water model necessitates the use of MARTINI-2 FF for the composite system. This liquid-liquid partitioning-based FF shows freezing and compaction of polymer chains near the clay surface, further accentuated by lowering of dispersive interactions between pairs of high-covalent-coordination ring units of TPS polymers and the montmorillonite sheet. A rescaling of the effective dispersive component of TPS-MMT cross interactions was used to optimize the MARTINI-2 FF for the composite system with structural (chain size distribution), thermodynamic (chain conformational entropy and density), and dynamic (self-diffusion coefficient) properties obtained from long AA simulations forming the constraints for optimization. The obtained CG FF parameters provided excellent estimates for several other properties of the melt and composite systems not used in parameter estimation, thus establishing the robustness of the developed model.

Entropy‐Driven Self‐Assembly of DNA Origami Isomers

Entropy can be an important factor to direct the self‐assembly of biomolecules into specific configurations, which requires repeatable and predictable design principles. Herein, a DNA origami system is presented, which folds into isomers with similar enthalpy but different conformational entropy due to loop formation of the scaffold, which is described quantitatively by an entropy model. It is demonstrated that the equilibrium distribution of a basic system consisting of two isomers can be tuned by changing the length, position, and number of scaffold loops, which is in good agreement with the model predictions. It is also shown that the folding pathway can be controlled kinetically through simple changes in the assembly protocol. Finally, a demonstration is done on how the equilibrium distribution of a more complicated system with six isomers can also be tuned in good agreement with model predictions. Overall, a new system and model for synthesizing nanoscale structures through predictable entropy‐driven self‐assembly of DNA origami is demonstrated. Given that the model is based on first principles, it is anticipated that the framework can be extended to the self‐assembly of other macromolecules such as proteins and RNA.

Stick-slip unfolding favors self-association of expanded HTT mRNA

In Huntington’s Disease (HD) and related disorders, expansion of CAG trinucleotide repeats produces a toxic gain of function in affected neurons. Expanded huntingtin (expHTT) mRNA forms aggregates that sequester essential RNA binding proteins, dysregulating mRNA processing and translation. The physical basis of RNA aggregation has been difficult to disentangle owing to the heterogeneous structure of the CAG repeats. Here, we probe the folding and unfolding pathways of expHTT mRNA using single-molecule force spectroscopy. Whereas normal HTT mRNAs unfold reversibly and cooperatively, expHTT mRNAs with 20 or 40 CAG repeats slip and unravel non-cooperatively at low tension. Slippage of CAG base pairs is punctuated by concerted rearrangement of adjacent CCG trinucleotides, trapping partially folded structures that readily base pair with another RNA strand. We suggest that the conformational entropy of the CAG repeats, combined with stable CCG base pairs, creates a stick-slip behavior that explains the aggregation propensity of expHTT mRNA.

Translocation of Gaussian polymers across a nanometric cylindrical channel

We present an analytical model to study translocation of Gaussian polymers across a cylindrical channel of nanometric size with a chemical potential inside the channel. Results show that polymer conformational entropy generates an entropic M-like free energy barrier for translocation. The presence of a small negative chemical potential reduces the entropic free energy barrier rendering the translocation time to follow a power law τ = AN ν as function of polymer size N. Power law exponents ν found here in varying the channel radius R, run from 1.525 to 1.999 for unforced translocation, and from 1.594 to 2.006 for translocation with small chemical potentials when R = 1 nm. Presence of large negative chemical potentials generate a free energy well rendering the translocation time to follow an exponential growth τ = Ae α N . We show existence of a negative chemical potential μ c that minimizes the translocation time due to an interplay of conformational entropy and channel-polymer interactions. The translocation time as function of channel length L grows exponentially as τ = Ae cL , it runs from milliseconds up to decades in the range of lengths found in biological channels. Interestingly, small negative chemical potentials approaching μ c overcome the effect of large channel lengths reducing the translocation time below seconds. Translocation speeds <v(N) > show a maximum of micrometers per second then it decays with polymer size and channel length, the characteristic decay <v(N) > ∼ N −1 has been observed in previous experiments of voltage-driven DNA translocation.

High Entropy Helps Na4Fe3(PO4)2P2O7 Improve Its Sodium Storage Performance

AbstractRecently, a high‐entropy strategy has attracted extensive attention and is applied to the preparation of electrode materials for energy storage batteries, aiming to improve electrochemical performance. It is found that adjusting the conformational entropy of the material can significantly enhance ion and electron transport efficiency, as well as improve the structural stability of the host material. However, there still remains a lack of deep understanding into the high‐entropy strategy, specifically regarding how this approach can alter the intrinsic properties of the material. In this work, the Na4Fe3(PO4)2P2O7 is designed and prepared as a model material with higher entropy, and ultimately, an optimized sample of Na3.9Fe2.6V0.1Mn0.1Cu0.1Mg0.1(PO4)2(P2O7) is achieved. The results indicate that increasing the entropy value of the material notably enhances its crystal structure, diffusion kinetics, and interfacial stability. Consequently, this optimized sample demonstrates deep insertion/extraction of 2.8 Na+, yielding an impressively high capacity of 122.3 mAh g−1 at 0.1C, alongside an ultra‐high rate capability of 100C. Remarkably, it also sustains performance over 14 000 cycles at 50C. This study underscores a method for fabricating high‐performance electrode materials through the implementation of the entropy strategy.

Reaction-Free Energies for Complexation of Carbohydrates by Tweezer Diboronic Acids.

The accurate calculation of reaction-free energies (ΔrG°) for diboronic acids and carbohydrates is challenging due to reactant flexibility and strong solute-solvent interactions. In this study, these challenges are addressed with a semiautomatic workflow based on quantum chemistry methods to calculate conformational free energies, generate microsolvated solute structural ensembles, and compute ΔrG°. Workflow parameters were optimized for accuracy and precision while controlling computational costs. We assessed the accuracy by studying three reactions of diboronic acids with glucose and galactose, finding that the conformational entropy contributes significantly (by 3-5 kcal/mol at room temperature). Explicit solvent molecules improve the computed ΔrG° accuracy by about 4 kcal/mol compared to experimental data, though using 13 or more water molecules reduced precision and increased computational overhead. After fine-tuning, the workflow demonstrated remarkable accuracy, with an absolute error of about 2 kcal/mol compared to experimental ΔrG° and an average interquartile range of 2.4 kcal/mol. These results highlight the workflow's potential for designing and screening tweezer-like ligands with tailored selectivity for various carbohydrates.

Recent progress in high‐entropy nanocatalysts

AbstractHigh‐entropy alloys (HEAs) are a promising group of materials composed of multiple elements (≥5) in nearly equal proportions (5 at%–35 at%), which exhibit uniformly mixed compositions and highly stable crystal structures and offer a wide range of design possibilities, making them exceptionally stable, multifunctional, and suitable for various applications. Recent research studies have identified the potential of HEAs as catalysts for electrocatalytic reactions, focusing on adjustable stress environments, optimizable d‐band centers, and high conformational entropy. Understanding the interactions among constituent elements, alloy formation, and catalytic reaction mechanisms is essential for optimizing HEAs' catalytic performance. This comprehensive review delves into the historical context, defining characteristics, and underlying significance of HEAs development. It also examines four primary effects of HEAs (high‐entropy effect, lattice distortion, sluggish diffusion, and cocktail effect) and their relevance to catalyst design criteria (selectivity, activity, stability, and cost). Additionally, it summarizes recent advances in nanostructured HEA catalyst synthesis, highlighting their advantages and challenges and explores the use of HEAs in electrocatalytic redox reactions involving small molecules (H, C, O, N). The paper underscores the importance of integrating experimental methods and theoretical calculations to design, synthesize, and understand alloy–property relationships of HEAs, emphasizing their vast potential for catalytic applications.

On the Stabilizing Effect of Aspartate and Glutamate and Its Counteraction by Common Denaturants.

By performing differential scanning calorimetry(DSC) measurements on RNase A, we studied the stabilization provided by the addition of potassium aspartate(KAsp) or potassium glutamate (KGlu) and found that it leads to a significant increase in the denaturation temperature of the protein. The stabilization proves to be mainly entropic in origin. A counteraction of the stabilization provided by KAsp or KGlu is obtained by adding common denaturants such as urea, guanidinium chloride, or guanidinium thiocyanate. A rationalization of the experimental data is devised on the basis of a theoretical approach developed by one of the authors. The main contribution to the conformational stability of globular proteins comes from the gain in translational entropy of water and co-solute ions and/or molecules for the decrease in solvent-excluded volume associated with polypeptide folding (i.e., there is a large decrease in solvent-accessible surface area). The magnitude of this entropic contribution increases with the number density and volume packing density of the solution. The two destabilizing contributions come from the conformational entropy of the chain, which should not depend significantly on the presence of co-solutes, and from the direct energetic interactions between co-solutes and the protein surface in both the native and denatured states. It is the magnitude of the latter that discriminates between stabilizing and destabilizing agents.

(Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3: A novel thermal barrier material with low thermal conductivity and excellent resistance to CMAS corrosion

High entropy ceramics are considered as promising materials for thermal barrier coatings due to phonon scattering caused by lattice distortion. In this study, perovskite high-entropy ceramics (Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3 (BSTZHS) were successfully prepared by dramatically increasing the conformational entropy of ceramics with complex crystal structures. The results showed that the sample exhibits a single-phase perovskite crystal structure with a dense surface, each element of the sample was uniformly distributed. Moreover, the thermal conductivity of (Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3 decreased significantly compared to SrZrO3 and BaZrO3 (the minimum thermal conductivity is 1.37 W/(m·K) at 273–1273 K). This study also identified descriptors for predicting the decrease in thermal conductivity of perovskite high-entropy ceramics. As well, the samples not only exhibit outstanding mechanical properties (Young’s modulus E = 255.7 ± 8.6 GPa、flexural strength Fb = 142.1 ± 4.8 MPa), but also good resistance to CMAS corrosion. Various results support that (Ba0.5Sr0.5)(Ti0.25Zr0.25Hf0.25Sn0.25)O3 is potential to be used for thermal barrier coatings.

Entropy enhancement drived high initial Coulombic efficiency and capacity integrated SnS2 nanosheets for lithium-ion batteries

Layer SnS2 has been garnered significant attention for next-generation lithium-ion batteries (LIBs), due to its abundant resources and high theoretical capacity. However, the low initial Coulombic efficiency, large volume expansion and structural degradation have significantly hindered its application in LIBs. Herein, the layer Sn0.7(MoFeCoNiV)0.3S2 nanosheets (HE3-SnS2) grown on the conductive substrate carbon cloth (CC) is synthesized by one-step hydrothermal method. Multiple elements doping strategy not only increases the conformational entropy which will improve the structural stability of during cycling, but also enlarges the interlayer spacing which benefits for lithium-ion transfer. As a result, the additive-free integrated CC@HE3-SnS2 electrode achieves a high reversible specific capacity of 1204.9 mAh g−1 with a high initial Coulombic efficiency of 94.7 % at 1C, and maintains 1011.4 mAh g−1 after 100 cycles. Specifically, the CC@HE3-SnS2 anode exhibits excellent rate capability of 670.8 mAh g−1 at 10C. Moreover, the full cell based on CC@HE3-SnS2 anode and commercial LiCoO2 cathode displays a stable capacity retention of 862.7 mAh g−1 after 100 cycles at 1C. The entropy-stabilized SnS2-based anode with high initial Coulombic efficiency and rate capability has a competitive candidate for LIBs.

Evolutionary analysis of ZAP and its cofactors identifies intrinsically disordered regions as central elements in host-pathogen interactions

The zinc-finger antiviral protein (ZAP) is an innate immunity sensor of non-self nucleic acids. Its antiviral activity is exerted through the physical interaction with different cofactors, including TRIM25, Riplet and KHNYN. Cellular proteins that interact with infectious agents are expected to be engaged in genetic conflicts that often result in their rapid evolution. To test this possibility and to identify the regions most strongly targeted by natural selection, we applied in silico molecular evolution tools to analyze the evolutionary history of ZAP and cofactors in four mammalian groups. We report evidence of positive selection in all genes and in most mammalian groups. On average, the intrinsically disordered regions (IDRs) embedded in the four proteins evolve significantly faster than folded domains and most positively selected sites fall within IDRs. In ZAP, the PARP domain also shows abundant signals of selection, and independent evolution in different mammalian groups suggests modulation of its ADP-ribose binding ability. Detailed analyses of the biophysical properties of IDRs revealed that chain compaction and conformational entropy are conserved across mammals. The IDRs in ZAP and KHNYN are particularly compact, indicating that they may promote phase separation (PS). In line with this hypothesis, we predicted several PS-promoting regions in ZAP and KHNYN, as well as in TRIM25. Positively selected sites are abundant in these regions, suggesting that PS may be important for the antiviral functions of these proteins and the evolutionary arms race with viruses. Our data shed light into the evolution of ZAP and cofactors and indicate that IDRs represent central elements in host-pathogen interactions.

Evolution of Virus-like Features and Intrinsically Disordered Regions in Retrotransposon-derived Mammalian Genes.

Several mammalian genes have originated from the domestication of retrotransposons, selfish mobile elements related to retroviruses. Some of the proteins encoded by these genes have maintained virus-like features; including self-processing, capsid structure formation, and the generation of different isoforms through -1 programmed ribosomal frameshifting. Using quantitative approaches in molecular evolution and biophysical analyses, we studied 28 retrotransposon-derived genes, with a focus on the evolution of virus-like features. By analyzing the rate of synonymous substitutions, we show that the -1 programmed ribosomal frameshifting mechanism in three of these genes (PEG10, PNMA3, and PNMA5) is conserved across mammals and originates alternative proteins. These genes were targets of positive selection in primates, and one of the positively selected sites affects a B-cell epitope on the spike domain of the PNMA5 capsid, a finding reminiscent of observations in infectious viruses. More generally, we found that retrotransposon-derived proteins vary in their intrinsically disordered region content and this is directly associated with their evolutionary rates. Most positively selected sites in these proteins are located in intrinsically disordered regions and some of them impact protein posttranslational modifications, such as autocleavage and phosphorylation. Detailed analyses of the biophysical properties of intrinsically disordered regions showed that positive selection preferentially targeted regions with lower conformational entropy. Furthermore, positive selection introduces variation in binary sequence patterns across orthologues, as well as in chain compaction. Our results shed light on the evolutionary trajectories of a unique class of mammalian genes and suggest a novel approach to study how intrinsically disordered region biophysical characteristics are affected by evolution.

Predictive Modeling of Nanocrystal Orientation in Superlattices: Insights from Ligand Entropy.

The self-assembly of nanocrystals (NCs) into close-packed, ordered superlattices (SLs) is of broad, engineering interest. The coherent orientation of polyhedral nanocrystals within NC SLs enhances electronic, magnetic, and vibrational coupling, leading to a variety of emergent phenomena. Here, we show that coherent orientation of polyhedral NCs in many SLs can be understood simply by considering its effect on the conformational entropy of surface ligands. We report the predicted nanocrystal orientations and entropic driving force to orient for a broad range of nanocrystal shapes and superlattice unit cells, and we show that ligand entropy is sufficient to reproduce a host of reported experimental and computational observations. We additionally use this framework to predict the expected distribution of interstitial species such as solvent or unbound ligands in an oriented NC SL. This work offers intuition for understanding the orientation of NCs in superlattices and a future framework for analyzing multinary structures.

Improvement of energy storage properties of NN-based ceramics by high-entropy strategy and A-site cation vacancies

High-entropy dielectric capacitors have recently drawn increasing attention in the field of energy storage. In this study, NiO has been incorporated into [(Na0.7Bi0.1)0.8Sm0.02Ca0.02Sr0.02Ba0.02]Nb0.8Sb0.1Ta0.1O3-based ceramics. We applied the concept of high-entropy design to introduce cation vacancies at the A-site, enhancing conformational entropy. This approach led to the successful preparation of a novel type of energy-storage ceramics with an ABO3 perovskite structure, denoted as (1-x)NBSCSBNST-xNiO (x = 0, 0.02, 0.04, & 0.06). We conducted a systematic study of the microstructural, dielectric, and ferroelectric characteristics, along with an exploration of the influence of the high-entropy strategy on their performance. The ΔSconfig increases with NiO doping, and the Eb of the NBSCSBNST-0.02Ni sample exhibits a significant increase to 730 kV/cm from 550 kV/cm of NBSCSBNSTN. This enhancement is accompanied by a recoverable energy density (Wrec) of 4.43 J/cm3 and an efficiency (η) of 75.9 %. As the content of NiO increases from x = 0 to x = 0.06, the phase transition diffusion behavior strengthens. Additionally, the permittivity (εr) spectrum becomes more uniform, and the activation energy of the prepared ceramic samples increases from 1.03 eV to 1.76 eV. This effect suppresses the emergence of localized electric branching, eventually improving the breakdown strength of NBSCSBNST-xNi ceramic materials. The obtained results indicate that the concept of high-entropy design to introduce cation vacancies at the A-site is an efficient approach to improve the energy storage characteristics of lead-free dielectric capacitors.

The entropy effect on the structure and microwave dielectric properties of high-entropy Lix(MgZnCoNi)(1-x)/4Al2O4-δ ceramics

In present study, high-entropy Lix(MgZnCoNi)(1-x)/4Al2O4-δ ceramics (x = 0.00–0.45) were synthesized using solid-state reaction route, which formed a single-phase spinel structure with a Fd-3m space group. The reduction in unit cell volume and lattice parameters were attributed to the compression of polyhedral structures. A moderate content of Li+ ions promoted the grain growth and improved the densification of ceramics. The internal connection among the conformational entropy (ΔSconfig), structure, and microwave dielectric properties in high-entropy Lix(MgZnCoNi)(1-x)/4Al2O4-δ ceramics was systematically studied. The dielectric constant (εr) was largely affected by the polarizability, and relatively high conformational entropy helped to increase the phonon vibrational energy and enhance the bond strength, resulting in low εr values. Additionally, the high concentration of oxygen vacancies, high packing fraction, low internal strain/fluctuation and suppressed damping behavior were closely related to relatively low conformational entropy. Notably, the introduction of oxygen vacancy leaded to the Al3+ ions preferentially occupy tetrahedral sites enhancing the covalency. These factors collectively reduced the intrinsic losses and improved the quality factor (Q×f). Moreover, relatively high conformational entropy conduced to the structural stability by improving the M-O (M = Li, Mg, Zn, Co, and Ni) bond strength and valence, which contributes to achieve near-zero temperature coefficient of resonant frequency (τf). As ΔSconfig changes, high-entropy Lix(MgZnCoNi)(1-x)/4Al2O4-δ ceramics presented great microwave dielectric properties: εr values of 5.46 ∼ 8.49, Q×f values of 3,540 GHz (f = 14.84 GHz) ∼ 56,950 GHz (f = 12.99 GHz), and τf values of −58 ppm/°C∼ −14 ppm/°C. Our study demonstrates that the high-entropy strategy effectively enhances microwave dielectric properties. This approach has potential applications across a broad spectrum of microwave dielectrics ceramics.

Exploring the Functional Landscape of the p53 Regulatory Domain: The Stabilizing Role of Post-Translational Modifications.

This study focuses on the intrinsically disordered regulatory domain of p53 and the impact of post-translational modifications. Through fully atomistic explicit water molecular dynamics simulations, we show the wealth of information and detailed understanding that can be obtained by varying the number of phosphorylated amino acids and implementing a restriction in the conformational entropy of the N-termini of that intrinsically disordered region. The take-home message for the reader is to achieve a detailed understanding of the impact of phosphorylation with respect to (1) the conformational dynamics and flexibility, (2) structural effects, (3) protein interactivity, and (4) energy landscapes and conformational ensembles. Although our model system is the regulatory domain p53 of the tumor suppressor protein p53, this study contributes to understanding the general effects of intrinsically disordered phosphorylated proteins and the impact of phosphorylated groups, more specifically, how minor changes in the primary sequence can affect the properties mentioned above.

Novel Insights into the Catalytic Mechanism of Collagenolysis by Zn(II)-Dependent Matrix Metalloproteinase-1.

Collagen hydrolysis, catalyzed by Zn(II)-dependent matrix metalloproteinases (MMPs), is a critical physiological process. Despite previous computational investigations into the catalytic mechanisms of MMP-mediated collagenolysis, a significant knowledge gap in understanding remains regarding the influence of conformational sampling and entropic contributions at physiological temperature on enzymatic collagenolysis. In our comprehensive multilevel computational study, employing quantum mechanics/molecular mechanics (QM/MM) metadynamics (MetD) simulations, we aimed to bridge this gap and provide valuable insights into the catalytic mechanism of MMP-1. Specifically, we compared the full enzyme-substrate complex in solution, clusters in solution, and gas-phase to elucidate insights into MMP-1-catalyzed collagenolysis. Our findings reveal significant differences in the catalytic mechanism when considering thermal effects and the dynamic evolution of the system, contrasting with conventional static potential energy surface QM/MM reaction path studies. Notably, we observed a significant stabilization of the critical tetrahedral intermediate, attributed to contributions from conformational flexibility and entropy. Moreover, we found that protonation of the scissile bond nitrogen occurs via proton transfer from a Zn(II)-coordinated hydroxide rather than from a solvent water molecule. Following C-N bond cleavage, the C-terminus remains coordinated to the catalytic Zn(II), while the N-terminus forms a hydrogen bond with a solvent water molecule. Subsequently, the release of the C-terminus is facilitated by the coordination of a water molecule. Our study underscores the pivotal role of protein conformational dynamics at physiological temperature in stabilizing the transition state of the rate-limiting step and key intermediates, compared to the corresponding reaction in solution. These fundamental insights into the mechanism of collagen degradation provide valuable guidance for the development of MMP-1-specific inhibitors.

A stable and low-fouling lead ion-selective electrode employing polyaniline-MXene composite for solid contact and polypeptide for antifouling

A biofouling-resistant solid-contact lead ion-selective electrode (Pb2+-ISE) with enhanced stability was developed based on dendritic peptides and polyaniline-MXene composites. The biofouling-resistant dendritic peptides, characterized by their high level of hydration and relative conformational entropy, effectively inhibit nonspecific adsorption. Simultaneously, the synergy between polyaniline nanowires and MXene nanosheets is harnessed to enhance the ion-electron transfer rate, thereby improving the stability of the ISE. The fabricated Pb2+-ISEs exhibit commendable electrochemical short-term stability and can rapidly respond to potential changes within 1 second. Under bacterial solution storage conditions, the peptide-modified ISEs maintain their Nernstian response without significant alteration for up to six days. Additionally, the Pb2+-ISEs are insensitive to O2, CO2, N2, and light, making them suitable for the analysis of Pb2+ in real complex samples. The strategic design incorporating dendritic peptides as a biofouling-resistant layer and the PANI-MXene composite as a conductive layer offers an effective approach to construct low-fouling ISEs capable of operating robustly in complex systems.

Shell with Striped, Helical, and Bipolar Lamellae Structures from Soft Confinement-Induced Self-Assembly of AB Diblock Copolymers on a Nanocylinder.

The soft confinement-induced self-assembly of AB diblock copolymers on a nanocylinder is studied via a simulated annealing method. The formation of multiple copolymer shells was predicted by varying the interfacial interaction, the size of confinement, and the height and diameter of the nanocylinder. The competition between solvent repulsion and nanocylinder attraction determined the degree of encapsulation of the copolymer shell. The formation of a helical copolymer shell was induced by the maximization of conformational entropy. The preferential distribution position of copolymers on anisotropic nanocylinder surfaces was induced by interfacial energy minimization. Our study contributes to the understanding of the formation mechanism of the helical structure in block copolymer aggregates and the fabrication of copolymer shells with predesigned morphologies.

Stick-slip unfolding favors self-association of expanded HTT mRNA.

In Huntington's Disease (HD) and related disorders, expansion of CAG trinucleotide repeats produces a toxic gain of function in affected neurons. Expanded huntingtin (expHTT) mRNA forms aggregates that sequester essential RNA binding proteins, dysregulating mRNA processing and translation. The physical basis of RNA aggregation has been difficult to disentangle owing to the heterogeneous structure of the CAG repeats. Here, we probe the folding and unfolding pathways of expHTT mRNA using single-molecule force spectroscopy. Whereas normal HTT mRNAs unfold reversibly and cooperatively, expHTT mRNAs with 20 or 40 CAG repeats slip and unravel non-cooperatively at low tension. Slippage of CAG base pairs is punctuated by concerted rearrangement of adjacent CCG trinucleotides, trapping partially folded structures that readily base pair with another RNA strand. We suggest that the conformational entropy of the CAG repeats, combined with stable CCG base pairs, creates a stick-slip behavior that explains the aggregation propensity of expHTT mRNA.