UHMWPE fibers exhibit impressive modulus and strength, but they have not reached their theoretical limits. Researchers focus on molecular weight, orientation, and crystallinity of UHMWPE, yet their contributions to mechanical properties are unclear. Molecular dynamics simulations are valuable but often limited by computational constraints. Our aim is to simulate higher molecular weights to better represent real UHMWPE fibers. We used Packmol and Polyply methodologies to construct PE systems, with Polyply reproducing more reasonable properties of UHMWPE fibers. Additionally, tensile simulations showed that orientation and crystallinity greatly impact Young's modulus more than molecular weight. Energy decomposition indicated that higher molecular weights lead to covalent bonds that can withstand more energy during stretching, thus increasing breaking strength. Combining simulations with machine learning, we found that orientation has the most significant impact on Young's modulus, contributing 60%, and molecular weight plays the most crucial role in determining the breaking strength, accounting for 65%. This study provides a theoretical basis and guidelines for enhancing UHMWPE's modulus and strength.

Proteins exert sophisticated functions through stimulus-responsive conformational changes. Mimicking this structural control and functional integration in synthetic, water-soluble polymers has been a fundamental challenge, largely due to the conflict between charge repulsion and conformational order. Here, we report a peptidomimetic polyelectrolyte that overcomes this limitation, maintaining stable and well-defined helical and sheet-like conformations across the entire physiological pH range despite its high charge density. This intrinsic conformational order creates through-space conjugated carbonyl clusters that function as non-classical chromophores, enabling excitation-dependent near-infrared fluorescence with an exceptionally large Stokes shift. More importantly, the sheet-like conformation enables cooperative, multidentate chelation of Fe3 + ions, which triggers an allosteric transition to a helix and results in nonlinear and ultrasensitive fluorescence quenching. Leveraging this unique "conformational transduction amplification" mechanism, we achieve real-time visualization and tracking of iron ion distribution and metabolic pathways at subcellular and whole-organism levels. This work establishes a paradigm of allosteric control in synthetic polyelectrolytes, opening avenues for the design of intelligent biomimetic materials for advanced sensing and imaging.

Phosphatidylcholine and its derivatives are highly attractive for their ability to enhance both the circulation stability and the cellular uptake of drug carriers. However, the mechanism underlying the phospholipid surface function and the impact of phospholipid density on micelle performance remain poorly understood. Here, we report the synthesis of a series of novel linear-dendritic copolymers based on phosphatidylcholine-polycaprolactone, where varying amounts of phosphatidylcholine groups can be attached to a single junction point at one end of the polycaprolactone. These copolymers self-assemble in aqueous solution to form micelles with different morphologies, demonstrating improved stability, drug loading capacity, and release behaviors with an increasing phospholipid content. Importantly, the micelles exhibit selective cellular uptake with a significant phospholipid dose dependence and show excellent antitumor efficacy in vivo at low drug dosages. This work provides a facile approach to designing and preparing nonlinear phospholipid copolymers with branched topology, offering a promising platform for drug delivery applications.

The elegant hierarchical structures of biomacromolecules have promoted the pursuits of synthetic polymers with ordered monomer sequences and diverse topological architectures, which are in the initial stage. Here, a four-arm star-shaped segmented polyurethane (PU) with a controlled block sequence of amphiphilic seven-segment multifunctional arms containing a disulfide bond was prepared via a grafting-onto strategy, where the sequence-defined arms were synthesized by a diisocyanate-based liquid-phase iterative methodology and then conjugated onto four alkyne-functionalized pentaerythritol cores through click chemistry. The star-shaped PU can self-assemble into micelles in aqueous solution as the linear arm. Moreover, the four-arm star-shaped architecture endows self-assembled micelles with higher stability under various physiological conditions and enhanced redox-responsive performance, making them promising candidates for drug delivery. The experiments show that drug-loaded star-shaped PU micelles possess accelerated stimuli-responsive release profiles, optimized tissue distribution, and improved anticancer efficacy in vitro and in vivo in comparison with linear polymer micelles. This work demonstrates that advanced architectures of precise linear polymers hold tremendous potential for the structural regulation and performance adjustment of aggregation structures, opening the perspectives for the structural and functional design of next-generation materials.

In biology, metal ions are fundamental to protein structure and function, directing folding through coordination chemistry and serving as active centers for catalysis, transport, and signaling. Synthetic poly(amino acids) (PAAs) are biomimetic polymers that combine exceptional tailorability and biocompatibility with well-defined secondary structures. The integration of metal ions with PAAs creates metallo-poly(amino acids) (MPAAs), where coordination to main-chain or side-chain ligands provides a powerful strategy to dictate conformational landscape and drive hierarchical self-assembly. This control, in turn, imbues the resulting supramolecular architectures with unique biological functions. This perspective systematically outlines the fundamental principles and strategies for manipulating PAA secondary structures and self-assembly via metal coordination. We then detail recent advances in MPAAs for applications in bioimaging, catalytic therapy, drug delivery, and biomimetic mineralization. Finally, we provide a critical perspective on the challenges and future research directions in this burgeoning field, highlighting the path toward rationally designed MPAAs for sophisticated biomedical and materials applications.

The healing of infected wounds is a formidable clinical challenge that demands advanced biomaterials capable of simultaneously eradicating pathogens and orchestrating the complex regenerative process. Herein, we engineered an immunomodulatory and angiogenic multifunctional hydrogel dressing by integrating choline phosphorylated chitosan (CS-MCP) with tetracycline-loaded polydopamine nanoparticles (PDA@TH NPs) for the programmed healing of infected wounds. This composite hydrogel demonstrates on-demand, spatiotemporally controlled therapeutic responses. Under near-infrared (NIR) irradiation, it enables synergistic bactericidal activity through photothermal effects and triggered antibiotic release. Moreover, the system exhibits pH-responsive drug release behavior, specifically targeting the acidic microenvironment of infected tissues. Beyond its potent antibacterial function, the hydrogel actively promotes regenerative processes. In vitro, CS-MCP markedly enhanced the adhesion, proliferation and tube formation of human umbilical vein endothelial cells, demonstrating potent pro-angiogenic effects. Furthermore, the polydopamine nanoparticles effectively scavenged reactive oxygen species (ROS), attenuating oxidative stress and inducing M2 macrophage polarization to foster an immunoregulatory microenvironment conducive to tissue repair. In a rat model of Staphylococcus aureus-infected full-thickness skin defects, the hydrogel significantly accelerated wound healing by comprehensively modulating the entire regeneration cascade: eliminating infection, mitigating inflammation, promoting angiogenesis, and enhancing collagen deposition. This study presents a novel immune-engaging and pro-regenerative strategy, representing a highly promising platform for the treatment of refractory infected wounds.

ABSTRACT In biological systems, enzymes achieve efficient catalysis by precisely assembling multinuclear metal‐oxo bridges, such as Fe─O─Fe motifs, under physiological conditions. However, constructing such structures in synthetic systems, particularly under mild aqueous conditions, remains challenging. Here, we report a self‐assembled helical polymer that creates a protein‐like microenvironment and enables the biomimetic construction of Fe─O─Fe structures in a synthetic polymer system under mild, neutral aqueous conditions. This strategy increases the stability constant of iron coordination by two orders of magnitude and endows the resulting complex with pH‐gated catalytic behavior: the complex remains catalytically inert under neutral conditions but exhibits more than 20‐fold enhanced peroxidase‐like activity in the weakly acidic tumor microenvironment. Moreover, oxo‐bridge formation significantly enhances near‐infrared absorption, enabling a robust photothermal effect. Without any exogenous drug payload, the complex selectively induces ferroptosis and immunogenic cell death in tumor cells, leading to complete tumor eradication in a mouse model. This work establishes a biomimetic strategy for constructing metal‐oxo‐bridged clusters and provides mechanistic insights into the structure‐function relationships of metalloprotein‐inspired materials.

Metal ion-mediated redox process and protein folding are fundamental to numerous physiological functions. However, the mechanisms underlying copper ion interactions with macromolecules remain insufficiently understood, and the therapeutic potential of polymer-copper complexes is largely underexplored. Here, a biomimetic metallopolymer is reported in which copper ion coordination induces a conformational transition from β-sheet to α-helix, accompanied by oxidative self-encapsulation and fluorescence quenching. By leveraging the tunable intrinsic fluorescence of the polymer, the first systematic elucidation of the coordination interaction mechanism between polythiols and copper ions is presented. This interaction enhances the structural stability, catalytic efficiency, membrane activity, and drug loading capacity. Furthermore, the polymer-copper complex demonstrates tumor-activated fluorescence and dual enzyme-mimetic activities, enabling precise tumor imaging and multimodal therapeutic efficacy both in vitro and in vivo. This work provides new insights into the interactions between macromolecules and metal ions and establishes a versatile and intelligent nanosystem for advanced disease diagnostics and therapeutics.

Inherent instability, low response efficiency, and lack of functionality have hindered the clinical application of polymer drug carriers. Addressing these challenges through straightforward molecular design remains a significant obstacle. Here, we introduce a novel approach using a structurally simple, clickable amphiphilic diblock copolymer vesicle. Our strategy involves asymmetric functionalized interfacial crosslinking, which modifies the interfacial curvature to induce polymersome swelling and stabilizes this metastable state through a disulfide-bond-crosslinked network, reminiscent of an inflated balloon. Moreover, the side chain functional groups of the crosslinking agent provide the self-assembled structures with controllable and switchable surface charges. This feature allows for the manipulation of nanoparticle internalization pathways, tissue distribution and tumor targeting efficacy in vivo. Notably, these functionalized balloon-like polymersomes can burst rapidly under the stimulation of glutathione, thereby facilitating efficient and specific intracellular drug release. This study presents an effective solution to the longstanding dilemma of stability, release, and functionality in diblock copolymer carriers, paving the way for the development of intelligent drug carriers with significant clinical translation potential.

Acute lung injury (ALI) is a prevalent and life-threatening condition lacking specific and effective treatments. To mitigate the inflammatory response within the ALI microenvironment, in this study a novel polyurethane (PCLSTU) was synthesized by using di-sulfide diisocynate and thioketal (TK) chain extender as the hard segment, which was used to prepare ROS-responsive anti-inflammatory nanoparticles (PCLSTU@PDA-CeO₂ NPs) loaded with polydopamine (PDA)-ceria NPs (CeO₂ NPs). In vitro studies demonstrated that the PCLSTU@PDA-CeO₂ NPs with a size of 400 nm exhibited enhanced ROS-scavenging activity under near-infrared (NIR) irradiation. Therapeutic efficacy was validated in a lipopolysaccharide (LPS)-induced ALI mouse model via nebulization inhalation and intravenous administration in vivo, where NIR irradiation significantly reduced lung edema and inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF). Comparatively, tail vein injection showed better therapeutic efficacy than the nebulization inhalation, highlighting their promise as a novel strategy for ALI treatment.

The weak intermolecular interaction and short-range aggregation endow organic semiconductors with the merits of flexibility, light weight, and solution processibility, while introducing more disorders at the same time. The greater degree of disorders in organic semiconductors, compared to inorganic semiconductors, is one of the major obstacles to their performance; thus, minimizing disorders is a key approach to boost the performance of organic electronics. Here, a strategy of using phthalate esters is introduced as assembly-inducing agents (AIAs) to improve the packing ordering of organic semiconductors, thereby reducing the energetic disorders and improving the device performance. With dioctyl phthalate AIA, the organic semiconductor PM6 shows a 24% reduction in Urbach energy, 11% narrower absorption full width at half maximum, and suppressed absorption tails in thin film. In organic field-effect transistors, this strategy offers a lift of hole mobility by 33.3%. In semitransparent organic photovoltaics, this strategy improves the average visible transmittance by 11.2% while maintaining the power conversion efficiency, yielding a high light utilization efficiency of 4.63% in optical structure-free devices. This work provides a facile and effective approach to suppress the energetic disorder of organic semiconductors and opens up a new avenue for fabricating high-performance organic electronics.

Dental plaque accumulates calcium and phosphorus ions from saliva and gradually mineralizes into calculus, a primary etiological factor of periodontal disease. The complex oral environment limits the efficacy of conventional antibacterial and anticalculus agents in preventing calculus formation. Inspired by statherin's mineral-binding properties, a peptide-polymer conjugate SNA6-PEG-TCS (DPT) was synthesized comprising a mineral-binding peptide (SNA6), antifouling polyethylene glycol (PEG) and antibacterial triclosan (TCS). DPT exhibits high water solubility and eradicates 88.71% of plaque while simultaneously inhibiting plaque formation and spontaneous precipitation of calcium/phosphorus ions. Additionally, DPT selectively binds to the enamel surface, forming a protective coating that blocks proteins, bacteria, and ionic deposition. Topical DPT application significantly reduces in vivo plaque formation while preserving oral microbiota homeostasis and causing no mucosal damage. This anticalculus mouthwash strategy offers a promising approach for clinical calculus prevention.

The secondary structures of polymers significantly influence their properties; however, understanding and modulating polymer conformations remain substantial challenges. Particularly, the β-turn conformation, which is prevalent in proteins, has not been reported in synthetic polymers due to its unclear formation mechanism and extremely poor stability. Additionally, there is a lack of visualization techniques to track conformational and functional transitions in polymers. Here, we designed and synthesized a novel tetraphenylethylene (TPE)-decorated poly(L-cysteine) derivative. Utilizing thioether oxidation as the driving force and strong aromatic-aromatic interactions between TPE molecules as stabilizing mechanism, we reported for the first time a conformational transition from β-sheet to β-turn in polymers. This transition not only significantly enhances fluorescence intensity but also induces chirality and circularly polarized light (CPL) of TPE, providing a new dual-modal approach to real-time monitoring of conformational changes of polymer chains. Furthermore, the conformational transition can trigger specific drug release, with the release process visualized and quantitatively analyzed through fluorescent colors. Such conformation-mediated structural and functional transformations hold significant potential for specific drug delivery and theragnosis of diseases such as cancer.

Polypeptide coacervates exhibit remarkable cell membrane permeability for drug delivery, but the precise internalization mechanism is unclear. Here, taking histidine-rich beak derivative protein (HBpep-SR) coacervate as a model, we investigate the interactions of coacervates with ternary lipid raft membranes and mammalian plasma membranes using the Martini 3.0 force field. We show that coacervates preferentially wet the liquid disordered (Ld) phase in a cholesterol-dependent manner with an encapsulation efficiency in the Ld phase of approximately 60%. In rigid, cholesterol-depleted ternary membranes, coacervates fail to induce membrane bending and disperse over time. Conversely, the flexibility of unsaturated lipids in the Ld phase of lipid rafts promotes coacervate wrapping, a process mediated by aromatic rings in polypeptides. Similar trends are observed in plasma membrane systems and other polypeptide coacervate systems. Our findings reveal a universal pathway for coacervate uptake via Ld regions, offering crucial insights for designing coacervates with enhanced cellular internalization.

Peptide-based coacervates are crucial for drug delivery due to their biocompatibility, versatility, high drug loading capacity, and cell penetration rates; however, their stability mechanism and phase behavior are not fully understood. Additionally, although Martini is one of the most famous force fields capable of describing coacervate formation with molecular details, a comprehensive benchmark of its accuracy has not been conducted. This research utilized the Martini 3.0 force field and machine learning algorithms to explore representative peptide-based coacervates, including those composed of polyaspartate (PAsp)/polyarginine (PArg), rmfp-1, sticker-and-spacer small molecules, and HBpep molecules. We identified key coacervate formation driving forces such as Coulomb, cation-pi, and pi-pi interactions and established three criteria for determining coacervate formation in simulations. The results also indicate that while Martini 3.0 accurately captures coacervate formation trends, it tends to underestimate Coulomb interactions and overestimate pi-pi interactions. What is more, our study on drug encapsulation of HBpep and its derivative coacervates suggested that most loaded drugs were distributed on surfaces of HBpep clusters, awaiting experimental validation. This study employs simulation to enhance understanding of peptide-based coacervate phase behavior and stability mechanisms while also benchmarking Martini 3.0, thereby providing fundamental insights for future experimental and simulation investigations.

Previous research showed that a peptide composed of three tyrosines (YYY) can turn into organic glass and cause strong adhesion between substrates via evaporation. However, the mechanisms of these processes remain unclear, and the exploration of applications of other peptide sequences is necessary. In this study, an optimized evaporation method was employed in molecular dynamics. It was found that YYY evaporation products possess abundant internal hydrogen bonds, which may facilitate the amorphous glass state formation. Moderate hydrophilicity of a peptide enhances molecular mobility and self-healing ability, while excessive hydrophilicity causes a water plasticizing effect. Stronger hydrophilicity also brings a larger curvature of evaporation products on polydimethylsiloxane (PDMS) substrate. A machine learning model was developed to predict the evaporation contact angle of peptide evaporation products and agrees well with the experiment. This research aims to improve understanding of peptide structure-function relationships and aid in designing custom organic optical devices based on peptide sequences.

Caries begin with an imbalance between demineralization and remineralization due to the continuous acid production by cariogenic bacteria. However, the development of dental materials that could prevent and treat caries via a simple and efficient mechanism has always been a challenge. To address this issue, therapeutic nanoparticles composed of a dendritic polyglutamic acid (DPGlu) and chelerythrine (CHE) complex (DPGlu@CHE) were developed via hydrophobic interactions and hydrogen bonds. DPGlu@CHE could be adsorbed onto the tooth surface, releasing CHE rapidly under acidic conditions to remove cariogenic bacteria, subsequently inducing tooth surface remineralization in situ. Our results demonstrated that more than 99% of Streptococcus mutans on the tooth surface were killed, and 84% of the mechanical properties of tooth were restored within 2 weeks. Thus, DPGlu@CHE was proven to be a safe and effective enamel restoration material in vitro, and its safety was verified in vivo, making it a promising mouthwash ingredient to maintain dental health.

By combining the lattice Boltzmann model of fluid flow with the molecular dynamics model of copolymers, we investigate the inertial migration of cylindrical micelles, which is obtained by controlling the length ratios of hydrophilic and hydrophobic segments in a comb-like copolymer. Our results demonstrate that cylindrical micelles gradually deviate from the center of the nanochannel with increasing Reynolds number (Re). For the same Re, the larger the cylindrical micelle is, the closer it is to the center of the nanochannel. Importantly, we find that the change in the equilibrium position is particularly pronounced at Re less than 0.1, while the trend becomes smoother at Re greater than 0.1, which is because of the transition of micelles from cylindrical to disk-like shapes when Re is smaller than 0.1, and does not change as Re further increases. This work provides an understanding of cylindrical micelles' inertial migration, particularly in identifying the effect of morphological changes on the equilibrium position, which could lead to significant advancements in the inertial migration of polymer micelles.

By using a series of mixed solutions composed of styrene oligomers (PSN, 10 < N < 550) and toluene, this work explores how the macromolecule crowding effects, including viscosity effect and conformational compression, regulates the flow-driven translocation, i.e., compression-induced fractionation (CIF), of polystyrene long chains (PS-1100k, 1.10 x 10(6) g/mol) through nanochannels (average pore radius r(0) approximate to 10 nm). The correlation between the macroscopic critical flow rate (Q(c)) and apparent viscosity (eta(app)) has been tested. Specifically, we have found the following: (1) eta(app) of PSN-toluene mixed solutions is found to be easily regulated in a broad range (0.52 <= eta(app) <= 5.02 mPa center dot s) by the oligomer strategy, which is beyond the window achieved by the small-molecule solvent system; (2) the translocation experiments in mixed solutions support the relation of Q(c) similar to 1/eta(app) predicted by de Gennes theory in the range of 0.52 mPa center dot s <= eta(app) <= 1.53 mPa center dot s, but a deviation is observed when 1.53 < eta(app) <= 5.02 mPa center dot s, implying the potential influence from the conformational compression of chains for CIF; (3) through a coarse-grained simulation on the blend system composed of a long chain (N-l = 100) and oligomer short chains (1 <= N-s <= 20) with varied volume fraction (phi(s)) from 0.1 to 0.4, the simulation result shows that the degree of compression of the long chain increases with N-s and phi(s) of oligomer short chains. Overall, the present study has preliminarily explored how the macromolecule crowding effects (viscosity effect and conformational compression) play the dominant role in regulating translocation behavior during the CIF process, which paves the foundation for understanding the transmembrane transport of biological macromolecules in the natural crowding cell environments.

Coacervates show promise in drug delivery systems due to their biocompatibility, versatility, and outstanding ability to penetrate cells. With the advent of all-atom (AA) and coarse-grained (CG) models, these computational tools function as ‘computational microscopes’, providing valuable insights to complement experimental research. This review covers the latest innovations in coacervate-based drug delivery systems. It summarizes the molecular properties and phase behavior of coacervates composed of polyelectrolytes, intrinsically disordered proteins (IDPs), and other biomolecules, along with their interactions with carried drugs and cell membranes. Additionally, this review highlights current challenges and limitations in this fast-moving field and proposes potential avenues for future research.