Enzymatic control of intermolecular interactions for generating synthetic nanoarchitectures in cellular environment DOI Creative Commons
Weiyi Tan, Qiuxin Zhang,

Mikki Lee

et al.

Science and Technology of Advanced Materials, Journal Year: 2024, Volume and Issue: 25(1)

Published: June 28, 2024

Nanoarchitectonics, as a technology to arrange nano-sized structural units such molecules in desired configuration, requires nano-organization, which usually relies on intermolecular interactions. This review briefly introduces the development of using enzymatic reactions control interactions for generating artificial nanoarchitectures cellular environment. We begin discussion with early examples and uniqueness enzymatically controlled self-assembly. Then, we describe intracellular nanostructures their relevant applications. Subsequently, discuss cases forming cell surface via reactions. Following that, highlight use creating intercellular nanostructures. Finally, provide summary outlook promises future direction this strategy. Our aim is give an updated introduction reaction regulating interactions, phenomenon ubiquitous biology but relatively less explored by chemists materials scientists. goal stimulate new developments simple versatile approach addressing societal needs.

Language: Английский

Electron Microscopy Studies of Soft Nanomaterials DOI
Zhiheng Lyu, Lehan Yao, Wenxiang Chen

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(7), P. 4051 - 4145

Published: Jan. 17, 2023

This review highlights recent efforts on applying electron microscopy (EM) to soft (including biological) nanomaterials. We will show how developments of both the hardware and software EM have enabled new insights into formation, assembly, functioning (e.g., energy conversion storage, phonon/photon modulation) these materials by providing shape, size, phase, structural, chemical information at nanometer or higher spatial resolution. Specifically, we first discuss standard real-space two-dimensional imaging analytical techniques which are offered conveniently microscopes without special holders advanced beam technology. The discussion is then extended advancements, including visualizing three-dimensional morphology nanomaterials using tomography its variations, identifying local structure strain diffraction, recording motions transformation in situ EM. On cover state-of-the-art technologies designed for overcoming technical barriers characterize as well representative application examples. even more integration machine learning impacts also discussed detail. With our perspectives future opportunities end, expect this inspire stimulate developing utilizing EM-based characterization methods atomic length scales academic research industrial applications.

Language: Английский

Citations

50
Enzyme Responsive Rigid-Rod Aromatics Target “Undruggable” Phosphatases to Kill Cancer Cells in a Mimetic Bone Microenvironment DOI
Meihui Yi, Fengbin Wang, Weiyi Tan

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(29), P. 13055 - 13059

Published: July 18, 2022

Bone metastasis remains a challenge in cancer treatment. Here we show enzymatic responsive rigid-rod aromatics acting as the substrates of "undruggable" phosphatases to kill cells mimetic bone microenvironment. By phosphorylation and conjugating nitrobenzoxadiazole (NBD) hydroxybiphenylcarboxylate (BP), obtained pBP-NBD (1P) substrate both acid alkaline phosphatases. 1P effectively kills metastatic castration-resistant prostate (mCRPCs) osteoblast mimic their coculture. enters Saos2 almost instantly target endoplasmic reticulum (ER) cells. Co-culturing with boosts cellular uptake by mCRPCs. Cryo-EM reveals nanotube structures (2.4 Å resolution, pH 5.6) 1 (2.2 7.4). The helical packing nanotubes is identical, held together strong pi-stacking interactions. Besides reporting atomistic structure formed assembly aromatics, this work expands pool molecules for designing EISA that selectively TME.

Language: Английский

Citations

46
Targeting Biomolecular Condensation and Protein Aggregation against Cancer DOI
Jerson L. Silva, Débora Foguel, Vı́tor F. Ferreira

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(14), P. 9094 - 9138

Published: June 28, 2023

Biomolecular condensates, membrane-less entities arising from liquid–liquid phase separation, hold dichotomous roles in health and disease. Alongside their physiological functions, these condensates can transition to a solid phase, producing amyloid-like structures implicated degenerative diseases cancer. This review thoroughly examines the dual nature of biomolecular spotlighting role cancer, particularly concerning p53 tumor suppressor. Given that over half malignant tumors possess mutations TP53 gene, this topic carries profound implications for future cancer treatment strategies. Notably, not only misfolds but also forms aggregates analogous other protein-based amyloids, thus significantly influencing progression through loss-of-function, negative dominance, gain-of-function pathways. The exact molecular mechanisms underpinning mutant remain elusive. However, cofactors like nucleic acids glycosaminoglycans are known be critical players intersection between diseases. Importantly, we reveal molecules capable inhibiting aggregation curtail proliferation migration. Hence, targeting transitions solid-like amorphous states offers promising direction innovative diagnostics therapeutics.

Language: Английский

Citations

37
Hierarchical assembly of intrinsically disordered short peptides DOI Creative Commons
Jiaqi Guo, Shane T. Rich-New, Chen Liu

et al.

Chem, Journal Year: 2023, Volume and Issue: 9(9), P. 2530 - 2546

Published: May 16, 2023

Language: Английский

Citations

28
Near-atomic-resolution structure of J-aggregated helical light-harvesting nanotubes DOI
Arundhati Deshmukh, Weili Zheng,

Chern Chuang

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(5), P. 800 - 808

Published: Feb. 5, 2024

Language: Английский

Citations

15
Atomic structures of naphthalene dipeptide micelles unravel mechanisms of assembly and gelation DOI Creative Commons
Ravi R. Sonani, Simona Bianco, B. Dietrich

et al.

Cell Reports Physical Science, Journal Year: 2024, Volume and Issue: 5(2), P. 101812 - 101812

Published: Jan. 31, 2024

Peptide-based biopolymers have gained increasing attention due to their versatile applications. A naphthalene dipeptide (2NapFF) can form chirality-dependent tubular micelles, leading supramolecular gels. The precise molecular arrangement within these micelles and the mechanism governing gelation remained enigmatic. We determined, at near-atomic resolution, cryoelectron microscopy structures of 2NapFF LL-tube LD-tube, generated by stereoisomers (l,l)-2NapFF (l,d)-2NapFF, respectively. reveal that fundamental packing dipeptides is driven systematic π-π stacking aromatic rings same-charge repulsion between carbonyl groups responsible for stiffness both tubes. structural analysis elucidates how a single residue's altered chirality gives rise markedly distinct sheds light on mechanisms underlying pH-dependent LL- LD-tubes. understanding provides insights rational design derivatives, enabling modulation micellar dimensions.

Language: Английский

Citations

10
Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity DOI Creative Commons
Thomas R. Fuerst, Alexander Marin, Sarah Jeong

et al.

Journal of Functional Biomaterials, Journal Year: 2025, Volume and Issue: 16(1), P. 34 - 34

Published: Jan. 19, 2025

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays important role in effort to prevent new infections. Supramolecular co-assembly co-presentation envelope E1E2 heterodimer complex core protein presents attractive design strategy for achieving humoral cellular immunity. With this objective, two antigens were non-covalently assembled with immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies characterized dynamic light scattering asymmetric flow field-flow fractionation methods directly visualized their vitrified state by cryogenic electron microscopy. vivo superiority VMPNs over individual components Alum-formulated manifests higher neutralizing antibody titers, promotion balanced IgG response, induction immunity—CD4+ T cell responses proteins. aqueous-based spontaneous immunopotentiating molecules enabled carrier offers simple pathway polymer-based supramolecular nanovaccine systems.

Language: Английский

Citations

1
DeepTracer-ID: De novo protein identification from cryo-EM maps DOI Creative Commons

Luca Chang,

Fengbin Wang,

Kiernan Connolly

et al.

Biophysical Journal, Journal Year: 2022, Volume and Issue: 121(15), P. 2840 - 2848

Published: June 28, 2022

Language: Английский

Citations

35
The current science of sequence-defined macromolecules DOI Creative Commons
Karen Hakobyan, Benjamin B. Noble, Jiangtao Xu

et al.

Progress in Polymer Science, Journal Year: 2023, Volume and Issue: 147, P. 101754 - 101754

Published: Oct. 20, 2023

A fundamental endeavour in macromolecular science is the control of molecular-level complexity, including molecular weight distribution, end groups and architecture. Since discovery that native biomacromolecules can have a specific sequence translating biological function, controlling individual monomer has become ultimate expression complexity. Replicating this remarkable structural precision abiological macromolecules emerged as defining goal challenge within polymer science. In Review, we survey developments synthetic methods, characterisation techniques, simulation workflows applications relevant to goal. We also address broader question what extent such complexity significant macromolecules. Specifically, will focus on Review because its importance connecting synthesis with applications.

Language: Английский

Citations

18
Phenol-soluble modulins PSMα3 and PSMβ2 form nanotubes that are cross-α amyloids DOI Creative Commons
Mark A. B. Kreutzberger, Shengyuan Wang, Leticia C. Beltrán

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(20)

Published: May 9, 2022

Phenol-soluble modulins (PSMs) are peptide-based virulence factors that play significant roles in the pathogenesis of staphylococcal strains community-associated and hospital-associated infections. In addition to cytotoxicity, PSMs display propensity self-assemble into fibrillar species, which may be mediated through formation amphipathic conformations. Here, we analyze self-assembly behavior two PSMs, PSMα3 PSMβ2, derived from peptides expressed by methicillin-resistant Staphylococcus aureus (MRSA), a human pathogen. both cases, observed mixture self-assembled species including twisted filaments, helical ribbons, nanotubes, can reversibly interconvert vitro. Cryo–electron microscopy structural analysis three PSM one revealed assemblies displayed remarkably similar structures based on lateral association cross-α amyloid protofilaments. The conformations PSMβ2 enforced bilayer arrangement within protofilaments defined respective nanotubes. We demonstrate that, amyloids cross-β protofilaments, these polymorphism, not only terms global morphology (e.g., filament, ribbon, nanotube) but also with respect number given peptide assembly. These results suggest folding landscape derivatives more complex than originally anticipated able sample wide range supramolecular space.

Language: Английский

Citations

24