Biomacromolecules最新文献

Synthesis of high-molecular-weight polypeptides and their block copolymer macromolecular architectures from β-sheet-promoting L-amino acids is still an unresolved problem. Here, an elegant steric hindrance-assisted ring-opening polymerization (SHAROP) strategy is introduced to access β-sheet poly(L-tyrosine) having more than 250 units. The scope of the synthetic methodology is expanded to access unexplored poly(L-tyrosine)-based higher-order β-sheet block copolymer nanoassemblies. In this strategy, a tert-butyl benzyl unit is employed as a steric handle that imbibes the solubility by promoting the α-helical conformation in the propagating polypeptide chains. The living ROP process enables the synthesis of well-defined block copolymers initiated by poly(L-tyrosine) living-chain ends or growing the poly(L-tyrosine) chains from the pre-existing macroinitiators of poly(L-glutamate) or poly(L-lysine). Acid-catalyzed postpolymerization deprotection restores the poly(L-tyrosine) blocks in their nascent β-sheet conformations. Thioflavin-T fluorescence assay establishes the β-sheet core-shell structures of these nanoassemblies, which are found to be nontoxic to mammalian cell lines.

We use a combination of Brownian dynamics (BD) simulation results and deep learning (DL) strategies for the rapid identification of large structural changes caused by missense mutations in intrinsically disordered proteins (IDPs). We used ∼6500 IDP sequences from MobiDB database of length 20-300 to obtain gyration radii from BD simulation on a coarse-grained single-bead amino acid model (HPS2 model) used by us and others [Dignon, G. L. PLoS Comput. Biol. 2018, 14, e1005941,Tesei, G. Proc. Natl. Acad. Sci. U.S.A. 2021, 118, e2111696118,Seth, S. J. Chem. Phys. 2024, 160, 014902] to generate the training sets for the DL algorithm. Using the gyration radii ⟨R_g⟩ of the simulated IDPs as the training set, we develop a multilayer perceptron neural net (NN) architecture that predicts the gyration radii of 33 IDPs previously studied by using BD simulation with 97% accuracy from the sequence and the corresponding parameters from the HPS model. We now utilize this NN to predict gyration radii of every permutation of missense mutations in IDPs. Our approach successfully identifies mutation-prone regions that induce significant alterations in the radius of gyration when compared to the wild-type IDP sequence. We further validate the prediction by running BD simulations on the subset of identified mutants. The neural network yields a (10⁴-10⁶)-fold faster computation in the search space for potentially harmful mutations. Our findings have substantial implications for rapid identification and understanding of diseases related to missense mutations in IDPs and for the development of potential therapeutic interventions. The method can be extended to accurate predictions of other mutation effects in disordered proteins.

Stimuli-responsive polymeric vehicles can change their physical or chemical properties when exposed to internal or external triggers, enabling precise spatiotemporal control of drug release. Nevertheless, systematic research is lacking in preparing dual stimuli-responsive amphiphilic block copolymers with different hydrophilic/hydrophobic block ratios in forming self-assembled structures. Here, we synthesized two types of block copolymers consisting of the hydrophobic segments (i.e., pH-responsive 2-(diethylamino)ethyl methacrylate (DEA) and ultrasound-responsive 2-methoxyethyl methacrylate (MEMA)) and hydrophilic poly(ethylene glycol) methyl ether (mPEG) segments, forming mPEG_X-b-P(DEA_Y-co-MEMA_Z). These amphiphilic block copolymers can self-assemble to form polymeric micelles, and their structures (e.g., size) and properties (e.g., critical vesicle concentration, stability, stimuli-responsiveness to pH and ultrasound, drug loading efficiency, and controlled drug release performance) were thoroughly investigated. In vitro cell studies further demonstrate that ultrasound can efficiently trigger drug release from polymeric micelles, emphasizing their potential for controlled drug delivery in therapeutic applications.

Cellulose nanocrystal (CNC) fillers have been shown to significantly improve the performance of polymer composites and hydrogels, elevating both strength and toughness. Polymer grafting from the surface of the nanocrystals has been employed to enhance matrix-filler interactions and keep the fillers dispersed within the matrix. However, such approaches often rely on multistep syntheses and diligent process control. Here, we propose modifying the nanocrystal surface to carry vinyl moieties, turning the particles into cross-linking comonomers. Using allyl glycidyl ether in an aqueous modification route, we were able to decorate the CNCs with varying amounts of vinyl moieties. Subsequent dispersion in 2-hydroxy methacrylate and thermally initiated free radical polymerization yielded composite materials that showed superior mechanical performance compared to those obtained from monomeric cross-linkers and unmodified CNCs. The large discrepancies in the observed glass transition temperatures of the obtained materials suggest, however, that the impact of the fillers on the polymerization kinetics is significant and less easily explained.

The extracellular matrix (ECM) plays a crucial role in organoid cultures by supporting cell proliferation and differentiation. A key feature of the ECM is its mechanical influence on the surrounding cells, directly affecting their behavior. Matrigel, the most commonly used ECM, is limited by its animal-derived origin, batch variability, and uncontrollable mechanical properties, restricting its use in 3D cell-model-based mechanobiological studies. Poly(2-alkyl-2-oxazoline) (PAOx) synthetic hydrogels represent an appealing alternative because of their reproducibility and versatile chemistry, enabling tuning of hydrogel stiffness and functionalization. Here, we studied PAOx hydrogels with differing compressive moduli for their potential to support 3D cell growth. PAOx hydrogels support spheroid and organoid growth over several days without the addition of ECM components. Furthermore, we discovered intestinal organoid epithelial polarity reversion in PAOx hydrogels and demonstrate how the tunable mechanical properties of PAOx can be used to study effects on the morphology and oxygenation of live multicellular spheroids.

Callose, a polysaccharide closely related to cellulose, plays a crucial role in plant development and resistance to environmental stress. These functions are often attributed to the enhancement by callose of the mechanical properties of semiordered assemblies of cellulose nanofibers. A recent study, however, suggested that the enhancement of mechanical properties by callose might be due to its ability to order neighboring water molecules, resulting in the formation, up to room temperature, of solid-like water-callose domains. This hypothesis is tested by atomistic molecular dynamics simulations using ad hoc models consisting of callose and cellulose hydrogels. The simulation results, however, do not show significant crystallinity in the callose/water samples. Moreover, the computation of the Young's modulus gives nearly the same result in callose/water and in cellulose/water samples, leaving callose's ability to link cellulose nanofibers into networks as the most likely mechanism underlying the strengthening of the plant cell wall.

The knowledge of the molecular properties and arrangements of biopolymers in both solid and solution state are essential in the design of sustainable materials and biomedicine as they are decisive for mechanical strength, flexibility, and biodegradability. However, the structure of most biopolymers at charged interfaces can vary considerably, and their time-dependent visualization in liquid-state still remains challenging. In this work, we employed high-speed atomic force microscopy (HS-AFM) to visualize single xylan macromolecules from alkali-extracted birch and beechwood. On negatively charged mica surfaces, they appeared as individual macromolecules but assembled into aggregates on 3-aminopropyltriethoxysilane (APTES) surfaces (AP-mica). Hence, we further investigated the susceptibility to enzymatic degradation using an endoxylanase, which showed that the individual xylan macromolecules remained intact, while larger assemblies on AP-mica degraded over time. We demonstrate that HS-AFM is a powerful tool for understanding the molecular properties and degradation mechanisms of biopolymers. Moreover, by identifying alignment-dependent binding sites, strategies can be developed to ensure the biodegradability of composite materials by intelligent interface design.

Protein-based materials can be engineered to derive utility from the structures and functions of the incorporated proteins. Modern methods of protein engineering bring promise of unprecedented control over molecular and network design, which will enable new and improved functionalities in materials that incorporate proteins as functional building blocks. For these advantages to be fully realized, there is a need for robust methods for producing protein-based networks, as well as methods for tuning their mechanical properties. Light-based 3D-printing techniques afford high-resolution fabrication capability with unparalleled design freedom in an inexpensive and decentralized capacity. This work features 3D-printed serum albumin-based bioplastics with mechanical properties modulated through the incorporation of glycerol or hyperbranched poly(glycerol)s (HPGs) as plasticizers. These materials capitalize upon important features of serum albumin, including its low intrinsic viscosity, high aqueous solubility, and relatively low cost. The incorporation of glycerol or HPGs of different sizes resulted in softer and more ductile bioplastics than those obtained natively without additives. These bioplastics showed shape-memory behavior and could be used to fabricate functional objects. These materials are accessible, possess minimal chemical hazards, and can be used for fabricating rigid and strong as well as soft and ductile parts using inexpensive commercial 3D printers.

The need for low-cost and effective antifouling solutions drives innovation in the fields of chemistry, materials science, and biology. In this work, guided by the antifouling strategies used by fluorescent corals, a series of fluorescent zinc acrylate polymer coatings containing coumarin units (ZAR-coumarin) was successfully prepared. The ZAR-coumarin coatings demonstrated excellent antifouling properties due to the synergistic action of multiple antifouling mechanisms, including fluorescent antifouling, natural bactericidal activity, and self-polishing surface renewal (due to ester group (-COO-Zn-OOC-) cleavage). Compared with zinc acrylate coatings without coumarin units (ZAR), the introduction of coumarin units significantly improved the inhibition efficiency for both bacteria and algae. In marine environment tests, the ZAR-AMCO-1, ZAR-ADMCO-1, and ZAR-CAMCO-1 coatings containing optimized amounts of different types of coumarin units maintained good antifouling properties over a 160-day field test period. This research presents an innovative approach to creating marine antifouling coatings.

Enzymatic degradation of plastics is a sustainable approach to address the growing issue of plastic accumulation. Here, we demonstrate the degradation of aliphatic polyesters using enzyme-displaying bacterial spores and the fabrication of self-degradable spore-containing plastics. The degradation proceeds without nutrient-dependent spore germination into living cells. Engineered spores completely degrade aliphatic polyesters into small molecules, retain activity through multiple cycles, and regain full activity through germination and sporulation. We also found that the interplay between the glass transition temperature and melting temperature of polyester substrates affects heterogeneous biocatalytic degradation by engineered spores. Directly incorporating spores into polyesters results in robust materials that are completely degradable. Our study offers a straightforward and sustainable biocatalytic approach to plastic degradation.