Aggregate (Hoboken, N.J.)最新文献

{"title":"In Situ Self-Assembled Molecular Fortifying Agent for Enhanced Retention and Therapeutic Efficacy of Radiopharmaceuticals","authors":"Daojia Liu,&nbsp;Xiaoqin Luo,&nbsp;Xiaojuan Wang,&nbsp;Xing Liu,&nbsp;Fanglei Zhang,&nbsp;Pan Wang,&nbsp;Jibin Song,&nbsp;Junqiang Chen","doi":"10.1002/agt2.70424","DOIUrl":"https://doi.org/10.1002/agt2.70424","url":null,"abstract":"<div>\u0000 \u0000 <p>Targeted radionuclide therapy is often limited by the rapid clearance of radiopharmaceuticals from tumor tissues, which reduces the delivered radiation dose and compromises therapeutic efficacy. To address this challenge, we developed a molecular-fortifying agent (MFA) strategy based on in situ self-assembly to extend the tumor retention of radioligands. This approach involves the intravenous administration of a DBCO-modified radioligand (¹⁷⁷Lu-FAPI-DBCO) for tumor-specific targeting, followed by injection of the MFA. Upon reaching the tumor microenvironment, the hydrophilic segment of MFA is cleaved by overexpressed fibroblast activation protein-α. The resulting exposure of the KLVFF motif alters the hydrophilic-hydrophobic balance, driving its rapid self-assembly via hydrophobic interaction and hydrogen bonding into dense nanofiber networks with abundant azide anchoring sites concentrated on the fiber surface. These nanofibers subsequently capture the pre-accumulated radioligands via a bio-orthogonal click reaction, covalently immobilizing them in situ. This assembly-induced retention effect significantly prolongs the intratumoral residence time of the radiopharmaceutical without increasing its accumulation in non-target organs. In a tumor model, the MFA strategy enhanced tumor retention, achieved an 88.7% tumor growth inhibition rate, and demonstrated favorable biosafety. Collectively, this strategy offers a promising and generalizable platform for improving the therapeutic profile of radiopharmaceuticals.</p>\u0000 </div>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 10","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Synuclein Aggregate-Disassembling Compounds Prolong Survival in a Mouse Model of Parkinson's Disease","authors":"Sara Reithofer,&nbsp;Marc Sevenich,&nbsp;Madita Vollmer,&nbsp;Dila Kurtul,&nbsp;Laura Müller,&nbsp;Pelin Özdüzenciler,&nbsp;Laurin Gerhards,&nbsp;Kira Allmeroth,&nbsp;Mathias Wendt,&nbsp;Fahimeh Charbgoo,&nbsp;Sarah Schemmert,&nbsp;Marcel Naumann,&nbsp;Karolina Korostov,&nbsp;Gina Hartmann,&nbsp;Lothar Gremer,&nbsp;Gültekin Tamgüney,&nbsp;Dieter Willbold,&nbsp;Antje Willuweit","doi":"10.1002/agt2.70439","DOIUrl":"https://doi.org/10.1002/agt2.70439","url":null,"abstract":"<p>Pathological aggregation of α-synuclein drives neuronal loss in Parkinson's disease. We therefore tested two optimized all-<span>d</span>-peptides, SVD-17 and SVD-1a, alongside the prototype SVD-1. Surface plasmon resonance revealed that SVD-17 binds monomeric α-synuclein with a nanomolar <i>K_D</i> of 1.09 nM. In vitro, SVD-17 and SVD-1a dismantled existing fibrils, rendering 50 % of them seeding-incompetent at 1.4 µM and 5.1 µM, respectively, and suppressed seeded aggregation in HEK293 α-synuclein biosensor cells with an IC₅₀ of 1.6 µM. Hemizygous TgM83^+/− mice received continuous subcutaneous infusion of each peptide for 3 months following intraperitoneal fibril seeding and were then monitored for neurological decline. Treatment with SVD-17 or SVD-1a extended median survival by 14% and 15%, whereas SVD-1 provided no significant benefit. Collectively, SVD-17 and SVD-1a bind α-synuclein with high affinity, disaggregate pathogenic assemblies, block further polymerization, and improve outcomes in a stringent in vivo model, underscoring their potential as disease-modifying therapeutics for Parkinson's disease and other synucleinopathies.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topological Engineering of Donor–Acceptor PDI-Based Conjugated Porous Polymers for Highly Efficient Discrimination of Methamphetamine and Amphetamine","authors":"Min Yu,&nbsp;Xu Cheng,&nbsp;Jiahao Dong,&nbsp;Chuanfang Zhao,&nbsp;Rongchao Zhu,&nbsp;Yadan Zhang,&nbsp;Baiyi Zu,&nbsp;Xincun Dou,&nbsp;Yincang Cui,&nbsp;Zhenzhen Cai","doi":"10.1002/agt2.70445","DOIUrl":"https://doi.org/10.1002/agt2.70445","url":null,"abstract":"<p>Topological engineering of conjugated porous polymers (CPPs) represents a pivotal pathway to optimize luminescence stability and sensing functionality yet establishing clear structure–property relationships remains a challenge. Here, a series of donor–acceptor type perylene diimide-based CPPs (D-A type PDI-based CPPs) with linear and networked topologies were designed by incorporating AIE-active fluorophores with varying bromine substitutions to alleviate the intrinsic aggregation-caused quenching (ACQ) of PDI units. Driven by multiple non-covalent interactions with CPPs, the PDI quenches via a synergistic mechanism of photoinduced electron transfer (PET) and the inner filter effect (IFE) when facing with analytes, while the AIE-active fluorophore keeps inert and the emission remains unchanged, resulting in an effective ratiometric fluorescence discrimination of methamphetamine (MA) and amphetamine (AMP). Specifically, the networked TPA-3-PDI achieves the largest interlayer stacking distance (14.58 Å), resulting in a prolonged fluorescence lifetime, enhanced quantum yields, and superior photostability, ultimately facilitating a superior sensing performance toward MA and AMP. Furthermore, the practicability of this design was validated by fabricating TPA-3-PDI-based sensing membranes, confirming the potential for real-time monitoring of trace-level gaseous MA and AMP in complex scenarios. This topological engineering strategy establishes a robust roadmap for the rational design of high-performance functional CPPs and advanced chemical sensing methodologies.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Building Block Architecture Regulates the Formation and Mechanical Performance of Depolymerizable Polymer Networks: An In Silico Study","authors":"Ji-Yuan Xing,&nbsp;Sheng Li,&nbsp;Er-Kang Wang,&nbsp;Jin Wang","doi":"10.1002/agt2.70440","DOIUrl":"https://doi.org/10.1002/agt2.70440","url":null,"abstract":"<p>Depolymerizable polymer networks are promising recyclable crosslinked materials that combine mechanical robustness with controlled post-use deconstruction. However, how changes in molecular building-block architecture propagate through network formation and internal organization to regulate macroscopic mechanical responses remains insufficiently understood. Here, using coarse-grained simulations, we systematically investigate how strand- and junction-level architectural parameters regulate network formation and mechanical performance in depolymerizable polymer networks. The simulated gel point occurs at higher conversion than predicted by Flory–Stockmayer theory, and the magnitude of this deviation depends on building-block architecture. Mechanically, deformation is governed by architecture-specific molecular mechanisms. Strand length regulates mechanical performance nonmonotonically through competing effects of conformational slack and effective-path density. Junction functionality regulates the strength–extensibility trade-off through a balance between effective network connectivity and local topological constraints, with the tetrafunctional network providing the best overall performance. Partial incorporation of bifunctional linkers further tunes extensibility by modulating network topology and delaying damage initiation. Together, these results establish hierarchical structure–property relationships that connect molecular building-block architecture with network formation, internal organization, and mechanical performance, providing molecular design principles for depolymerizable polymer networks.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Color-Tunable Organic Room-Temperature Phosphorescence From Single-Luminophore Aggregation in Polymer","authors":"Qingyun Jiang,&nbsp;Huili Yang,&nbsp;Lilin Wang,&nbsp;Yu Lang,&nbsp;Chunxiong Zheng,&nbsp;Zhenguo Chi,&nbsp;Jiadong Zhou,&nbsp;Cong Liu,&nbsp;Bingjia Xu,&nbsp;Guang Shi","doi":"10.1002/agt2.70444","DOIUrl":"https://doi.org/10.1002/agt2.70444","url":null,"abstract":"<p>Organic room-temperature phosphorescence (ORTP) materials with tunable afterglow colors are highly desirable for advanced optoelectronic applications. Herein, color-tunable ORTP materials were achieved by simply doping different concentrations of a single luminophore into a melamine-formaldehyde (MF) polymer matrix. The doped luminophores (Me2-BCF and Spiro-BCF), which feature a planar π-conjugated core and sterically hindered side groups, were designed to exhibit a distinctly low critical aggregation concentration. The states of Me2-BCF and Spiro-BCF in the MF polymer matrix can be precisely tuned from dispersed monomers to different stacked dimers by varying their doping concentrations. ORTP materials with a tunable afterglow color transition from green to orange–red and a phosphorescence lifetime exceeding one second were realized, and they displayed good performance in information encryption. This work provides fundamental insights into aggregation-controlled luminescence and offers a versatile pathway toward color-tunable ORTP materials.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Synergistic Nanotherapeutic Platform Leveraging Bioorthogonal Amplification and Ultrasound Triggering for Multidrug-Resistant Bacterial Clearance and Wound Repair","authors":"Wentao Lei,&nbsp;Binbin Fu,&nbsp;Cuizhou Luan,&nbsp;Jinhao Li,&nbsp;Sijia Huang,&nbsp;Jianping Shao,&nbsp;Zifei Wang,&nbsp;Shufen Ye,&nbsp;Zhengyin Pan,&nbsp;Liang He","doi":"10.1002/agt2.70443","DOIUrl":"https://doi.org/10.1002/agt2.70443","url":null,"abstract":"<p>The rise of multidrug-resistant (MDR) bacterial infections highlights the need for precise, non-antibiotic therapeutic strategies. Herein, a bioorthogonal reaction-mediated and ultrasound (US)-responsive nanoplatform (denoted as MnCyNPs-Tz) was developed for synergistic antibacterial therapy. The platform encapsulates a multifunctional tricarbonyl Mn(I)-cyanine complex (Mn-Cy7) within tetrazine (Tz)-functionalized DSPE-PEG₂₀₀₀. Its targeting mechanism relies on a two-step process: bacteria are first pre-labeled with <i>trans</i>-cyclooctene-polyethylene-glycol₄-phenylboronic acid (TCO-PBA), enabling rapid, covalent, and enhanced anchoring of MnCyNPs-Tz via the Tz-TCO bioorthogonal reaction. DFT calculations indicated that incorporation of the IR-780 ligand facilitates US-triggered generation of hydroxyl radicals (·OH) and release of carbon monoxide (CO), underpinning a synergistic Type-I sonodynamic and gas therapy. In vitro, the targeted system demonstrated potent efficacy against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) by disrupting bacterial membranes and biofilms. Transcriptomic analysis revealed that it selectively interferes with bacterial oxidative stress responses, disrupts the respiratory chain and energy metabolism, and impairs membrane integrity, without inducing antibiotic resistance. In a murine MRSA-infected wound model, US activation of the platform reduced bacterial burden (∼1% survival rate) and accelerated wound repair, achieving 99.1% closure within 10 days, alongside promoted tissue regeneration. This work presents a bioorthogonal reaction-amplified, US-activated strategy as a precise and effective antibiotic-free alternative against MDR infections.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationally Designed AIE Small Molecule Enabling NIR‑II Absorption and Multimodal Phototheranostics for Orthotopic Colon Cancer Treatment","authors":"Miaomiao Kang,&nbsp;Zengming Yang,&nbsp;Jun Zhu,&nbsp;Hao Yang,&nbsp;Shuaiyin Zhang,&nbsp;Zhijun Zhang,&nbsp;Xue Li,&nbsp;Dong Wang,&nbsp;Ben Zhong Tang","doi":"10.1002/agt2.70441","DOIUrl":"https://doi.org/10.1002/agt2.70441","url":null,"abstract":"<p>“One-for-all” phototheranostics, wherein a single-component molecule aggregate simultaneously integrates multiple optical imaging and therapeutic modalities, have emerged as highly attractive strategies for oncotherapy. Aggregation‑induced emission luminogens (AIEgens) have been proven to be ideal templates for developing such versatile systems, owing to their inherent superiority in finely balancing competing excited‑state energy dissipation pathways. Despite this significant advantage, achieving multimodal phototheranostic AIEgens with absorption in the second near‑infrared (NIR‑II, 1000–1700 nm) window remains a fundamental challenge, due to the intrinsic trade‑off between molecular planarity and twisting. Given the deep tissue penetration and high maximum permissible exposure associated with NIR‑II light, we herein constructed the first NIR‑II‑absorbing “one-for-all” phototheranostic AIEgen, named OTDTB, by concurrently harnessing the intrinsic versatility of AIEgens and leveraging donor–acceptor modulation, bond vibration, and alkyl chain engineering. Following formulation into nanoparticles (NPs), OTDTB NPs exhibit an emission peak at 1274 nm, satisfactory reactive oxygen species generation ability, and a high photothermal conversion efficiency of 71.5% under 1064 nm excitation. Coupled with excellent photostability and biosafety, OTDTB NPs well-performed in 1064 nm-excitable fluorescence–photoacoustic–photothermal trimodal imaging and synergistic photodynamic–photothermal therapy in colon cancer models. Overall, this work offers valuable design philosophy for constructing NIR‑II‑absorbing “one‑for‑all” phototheranostic platforms.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hierarchical Assembly as a Design Principle: Structure–Property Relationships Linking Biological Architectures to Functional Aggregate Materials","authors":"Nafeesa Sarfraz,&nbsp;Sadaf Bibi,&nbsp;Muhammad Ibrar Ahmed,&nbsp;Jawad Hussain,&nbsp;Shahid Iqbal,&nbsp;Imran Mahmood Khan,&nbsp;Ajayan Vinu,&nbsp;Ibrahim Khan","doi":"10.1002/agt2.70436","DOIUrl":"https://doi.org/10.1002/agt2.70436","url":null,"abstract":"<p>Biological systems solve energy conversion, fluidic, mechanical, and optical problems using hierarchically ordered architectures whose functional feature sizes fall in the nanometer-to-micrometer range. Translating these architectures into synthetic devices requires transferable design rules rather than morphological analogy. Here, we examine five mature biomimetic technologies through a single mechanistic lens. This involves the relationship between hierarchical feature size and the physical process it controls. We analyze (i) Z-scheme and S-scheme photocatalysts that reproduce the two-photosystem charge relay of plant photosynthesis, in which band alignment across nanoscale heterojunction interfaces governs carrier separation and supports hydrogen evolution rates exceeding 70 mmol g⁻¹ h⁻¹. Then, we highlight (ii) shark denticle and pitcher-plant surfaces, in which micrometer-scale riblet spacing combined with superimposed nanotexture and lubricant-retaining nanoporosity sets turbulent wall shear and yields drag reductions of 10%–17%. Also, (iii) spider silk and its synthetic analogues, in which the β-sheet nanocrystal-to-amorphous-matrix ratio dictates a strength–toughness envelope reaching 895 MPa and 370 MJ m⁻³ are also elucidated. Moreover, (iv) chameleon-derived photonic skins, in which colloidal nanocrystal lattice spacing tunes reflectance across 480–683 nm with millisecond mechanochromic response, are highlighted. Finally, (v) soft actuators built from liquid metals, hydrogels, and shape-memory polymers, in which nanoscale filler dispersion and crosslink density set actuation strain and rate, are discussed. For each system, we tabulated reported performance against its biological benchmark, identified where the synthetic replica underperforms and why, and separated design rules that transfer between systems from those that do not. Hierarchical order across at least two length scales, interfacial gradient engineering, and stimulus-coupled anisotropy emerge as the three transferable rules.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand-Free All-Metal Super-Chalcogens Stabilized by Jellium-Guided Charge Engineering in Group 13 Zintl Superlattices","authors":"Jun Li,&nbsp;Shi-Hu Du,&nbsp;Shi-Jun Wang,&nbsp;Peigeng Han,&nbsp;Lei Zhang,&nbsp;Jing Chen,&nbsp;Yuxiang Bu,&nbsp;Shi-Bo Cheng","doi":"10.1002/agt2.70431","DOIUrl":"https://doi.org/10.1002/agt2.70431","url":null,"abstract":"<p>While considerable progress has been made in synthesizing ligand-free all-metal clusters (LFAMCs) for Groups 14 and 15 within the Zintl phase, achieving stable condensed-phase analogues for electron-deficient Group 13 metals remains a significant and unresolved challenge. Herein, we overcome this challenge through a jellium-guided charge-engineering strategy that transcends classical Zintl principles, such as the Wade–Mingos and octet rules. By leveraging structure-directing cations to tune lattice charge, we stabilize a series of ligand-free super-chalcogens, BeM₁₂ (M = Al, Ga, and In), achieving the jellium-predicted 40-electron closed-shell configuration exclusively via ionic interactions. The resulting superatomic CdI₂-type superlattice, BeM₁₂[Y(2,2,2-crypt)]₂ (Y = Na, K, Rb, and Cs), exhibits exceptional stability, linearly tunable bandgaps, strong visible-light absorption, a pressure-dependent optoelectronic response, and a record-low exfoliation energy that facilitates straightforward 2D fabrication. Crucially, this superlattice inherits the energetically and spatially separated frontier orbital character of its parent cluster, manifesting electronic behavior unprecedented in conventional ionic materials. A jellium-based shell-closing transition (38 → 40 electrons) underpins the assembly, thereby extending the established framework of Zintl-phase electronic theory. This work establishes a general design principle for stabilizing highly reactive LFAMCs and opens a promising avenue for developing quantum-confined functional materials.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stage-Dependent Signatures of Tau K18 Fibril Growth and Maturation Revealed by Tip-Enhanced Raman Spectroscopy","authors":"Marta Urbańska,&nbsp;Katarzyna Skirlińska-Nosek,&nbsp;Ewelina Lipiec,&nbsp;Kamila Sofińska","doi":"10.1002/agt2.70434","DOIUrl":"https://doi.org/10.1002/agt2.70434","url":null,"abstract":"<p>Tau protein aggregation is one of the key pathological processes driving the global burden of dementia, with Alzheimer's disease being its leading cause. Research on the aggregation pathways and fibrillar structures could provide key insights into the pathogenesis and potential therapeutic approaches for dementia-related disorders. Despite extensive studies of tau aggregation, the nanoscale chemical and structural heterogeneity of tau fibrils during their maturation remains poorly understood. In particular, early aggregation intermediates, fibril-to-fibril variability, secondary nucleation processes, and differences at the molecular level between truncated and full-length tau fibrils have not been directly resolved due to limitations in spatial resolution and chemical sensitivity of conventional analytical techniques. In this study, we focus on the stage-dependent fibrillization of the tau K18 fragment using an extremely sensitive nanospectroscopic technique, tip-enhanced Raman spectroscopy (TERS) that provides chemical information with nanometer spatial resolution. Single-point TER spectra provide insights into the structural transitions related to tau K18 maturation at the level of individual fibrils. Our findings indicate that TERS directly differentiates K18 from full-length tau fibrils at early fibrillization stages, revealing the impact of the fuzzy coat on aggregation pathways. Additionally, we show that TER hyperspectral imaging enables direct visualization of the ongoing secondary nucleation process. Finally, our findings reveal the stage-specific roles of amino-acid side chains, indicating that histidine is involved in the initial aggregation and secondary nucleation processes, whereas phenylalanine and tyrosine contribute to the stabilization of β-sheet architecture.</p>","PeriodicalId":72127,"journal":{"name":"Aggregate (Hoboken, N.J.)","volume":"7 9","pages":""},"PeriodicalIF":13.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/agt2.70434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}