Biomacromolecules最新文献

Self-supporting bilayer films were produced by combining a protein (casein or gelatin) and a polysaccharide (carboxymethylcellulose, CMC). Effective interfacial interactions, achieved either physically (primarily via electrostatic interactions) or chemically (with citric acid and 1,2,3,4-butanetetracarboxylic acid (BTCA) as cross-linkers), granted improved mechanical and functional performance. Gelatin layers exhibited strong adhesion across different pH values (3, 4.5, and 8), indicating a minimal role of electrostatic forces in interlayer interactions. In contrast, casein required the incorporation of tannic acid (TA) into the CMC layer as a compatibilizing agent to achieve effective adhesion. Polysaccharide cross-linkers were evaluated in casein-CMC bilayers, where citric acid reduced the water absorption, while BTCA improved water vapor barrier properties but decreased mechanical resistance. Understanding interfacial interactions enables the design of biobased materials with tailored properties, boosting competitiveness and functionality within the circular bioeconomy.

In this work, the ice-inhibiting effects and their underlying mechanisms of inulin with various chain lengths were elucidated through experimental measurements and molecular dynamics simulations. The results suggested that long-chain inulin (HP group) exhibited strong and stable ice-inhibiting effects, with a minimum %MGS (12.18%) and limited ice growth of 36.61% after 100 min of freezing. The extensive contact area of long-chain inulin with water molecules (higher R_g and solvent-accessible surface area (SASA) values) favored their hydrogen-bond formation, which further disrupted the original hydrogen-bonding network of water by transforming the hydrogen-bonding mode (DDAA-OH mode into the DA mode). The remarkable cryoprotective effects of the HP group on scallops were evidenced by no significant difference in mass loss, water-holding capacity (WHC), and structural stability of the myofibrillar protein with the commercial antifreeze group (p > 0.05). This study provides strong evidence to broaden the cryoprotection applications of inulin to improve the quality of frozen food.

The persistence of cancer stem cells (CSCs) within deep tumors is a primary driver of therapeutic failure and relapse. Most large nanoparticles fail to penetrate deep tumors, and extra-small nanoparticles suffer from poor retention in tumors. To solve the "penetration-retention paradox", herein, we developed special extra-small iron oxide nanoparticles (IO) featuring an "AND logic-gate"-driven self-assembly to achieve both deep penetration and long retention in large tumors for efficient CSCs dismission. Typically, the poly(ethylene glycol) (PEG) shield of IO is functionalized with a tyrosine (T) and thioketal (TK) linker followed by β-lapachone (LAP) loading, forming TIO-TK-PEG@LAP. (i) The extra-small TIO-TK-PEG@LAP can penetrate into deep tumors, whose H₂O₂ cleaves the TK linker, detaching the PEG shield and exposing T residues. (ii) The H⁺ facilitates the release of Fe²⁺ from IO to react with H₂O₂, generating hydroxyl radicals (^•OH). (iii) The ^•OH catalyzes covalent cross-linking of T residues, driving in situ self-assembly into IO aggregates (∼100 nm), prolonging tumor retention. (iv) After cellular uptake, the IO aggregates are degraded in the endosomes, releasing LAP and Fe²⁺. (v) LAP can be catalyzed to generate substantial H₂O₂, which synergizes with Fe²⁺ to amplify the Fenton reaction, generating explosive ^•OH to trigger ferroptosis of tumor cells.

Enzyme-encapsulated nanogels serve as promising platforms for constructing enzyme nanoreactors in which mass transport plays a crucial role in the enzymatic performance. However, it remains a challenge to investigate the relationship between the permeability of nanoreactors and their catalytic efficiency owing to their small dimensions. The molecular permeability behavior and enzyme activity of two types of nanogels with different hydrophobicities are compared using 8-anilinonaphthalene-1-sulfonic acid (ANS) fluorescence assays. Partitioning experiments with different fluorescent dyes demonstrate that hydrophobic and electrostatic interactions govern the molecular distributions within the nanogels. Total internal reflection microscopy (TIRF) further demonstrates that a less hydrophobic microenvironment facilitates the faster mass transport of hydrophobic resorufin molecules. This contributes to the higher catalytic activity and greater reaction heterogeneity observed in the single-particle assays. These results underscore the importance of hydrogel molecular permeability in modulating enzyme kinetics and offer valuable insights into the rational design of efficient enzyme nanoreactors.

Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics due to their rapid bactericidal actions via membrane disruptions, making it difficult for pathogenic microbes to develop antimicrobial resistance (AMR). This work reported that lipopeptides rich in Arginine (R) and Tryptophan (W), namely, C₁₂RRWW, C₁₂WWRR, and C₁₂RWWR, where C₁₂ denotes a lauroyl chain, were antimicrobial against resistant and clinically isolated Escherichia coli and Staphylococcus aureus strains, with C₁₂RRWW achieving a high potency against S. aureus and E. coli and fast eradication of Pseudomonas aeruginosa compared to polymyxin B. Neutron reflection (NR) and small-angle neutron scattering (SANS) unravelled structural disruptions to the bacterial membranes that were well correlated to the antimicrobial actions observed from fluorescent and antimicrobial assays. This work demonstrates the power of NR and SANS at revealing the eradications of different pathogens via selective bacterial membrane targeting, crucial to the rational design of new AMPs for the control of AMR outbreak.

The development of rapid, chemoselective covalent bond-forming reactions enables the assembly of hydrogel scaffolds suitable for applications in cellular encapsulation. We previously reported that amide-forming ligations between potassium acyltrifluoroborates (KATs) and hydroxylamines produce robust hydrogels that have excellent cytocompatibility, but the requirement for somewhat acidic conditions for efficient hydrogel assemblies limited their application to robust cell types. To overcome this constraint, we have recently found that quinolinium acyltrifluoroborates (QATs) serve as highly efficient reaction partners for amide-forming reactions at neutral pH. In this article, we document the construction of poly(ethylene glycol) (PEG)-derived hydrogels by efficient cross-linking of QAT-functionalized macromers with a partner hydroxylamine-functionalized macromer. Gelation occurs at physiological pH in under 2 min, offering a rapid and facile approach to the immobilization of delicate stromal cells. The cytocompatibility of the cross-linking was demonstrated by in situ gelation in the presence of human mesenchymal stem cells and sustained cell viability for 7 days. Facile incorporation of a cyclic cell adhesion peptide, simply by including the reaction partner in the gelation reactions, illustrated that the desired components can be introduced into the gels without further elaboration.

Mutations in the tumor suppressor p53, particularly the R273 mutation, are major drivers of poor prognosis and treatment resistance in colorectal cancer (CRC). Additionally, reports have recently shown that environmental factors and metabolites within the tumor microenvironment act together to drive and compound tumor progression. This study investigates the interactions between secondary bile acids, lithocholic acid (LCA), and deoxycholic acid (DCA), and mutant p53 in CRC. We show that while the secondary bile acids have a minimal effect on wild-type p53, it significantly promotes the aggregation of the R273H and R273C mutant variants, an effect that is markedly enhanced in the presence of the chemotherapy drug doxorubicin in cell lines. Our biophysical studies demonstrate that the DNA binding is compromised in mutant p53 and is completely lost in the presence of the bile acids and doxorubicin. Further, we show that LCA binds to mutant p53 with high affinity, inducing the formation of large oligomeric assemblies and biomolecular condensates. Binding studies reveal stronger interactions between the bile acids and mutant p53, resulting in increased aggregation, as confirmed by imaging studies. Additionally, bile acids induce biomolecular condensate formation in mutant p53, sequestering doxorubicin within these structures and suggesting a mechanism for chemoresistance. These findings highlight the role of bile acids in promoting mutant p53 aggregation and therapy resistance, suggesting potential new therapeutic targets for p53 mutant CRC.

Hydration modulates the adhesion of cellulosic plant-seed mucilage to substrates. Using coarse-grained many-body dissipative particle dynamics (MDPD), we show the synergistic adhesion of hydrated cellulose; the adhesion of the water-cellulose mixture is stronger than the weighted average of the two components. At low to moderate hydration, water plasticizes the stiff cellulose chains, making them more flexible and better able to adapt to the substrate during retraction. We show this by artificially modifying dry cellulose so that its flexibility matches that of hydrated cellulose. Thus, softened dry cellulose has the same pull-off force as the unchanged, but hydrated cellulose. More support for the softening mechanism being responsible for increased adhesion is that it can also be brought about by small molecules other than water: Mixing in cellulose monomers or dimers improves adhesion, but the admixture of longer oligomers does not. For comparison, we also investigated pectin mucilages, pectin being the other important component of seed mucilage. Here, there is no synergy between water and pectin, with the effect being additive at best. Blending cellulose with pectin increases adhesion because pectin is inherently more flexible and has a higher baseline stickiness, yet the effect remains additive.

The integration of excellent performance and facile closed-loop recycling of poly(butylene terephthalate) (PBT) copolyesters remains a significant challenge. Herein, a biobased rigid diol (denoted as HT) was prepared by an acid-catalyzed acetalization reaction from 5-hydroxymethylfurfural (HMF) and trimethylolpropane (TMP). HT was copolymerized with PBT to prepare a series of PBT_xTT_y copolyesters with high M_n up to 45.5 kDa. The insertion of HT led to excellent thermomechanical and UV shielding properties, such as the glass transition temperature (T_g of 47.3 °C) and strength (43 MPa) of PBT₈₀TT₂₀ outdistancing those of PBT. More importantly, the acetal-based HT enabled dual closed-loop recycling pathways for PBT_xTT_y copolyesters via selective cleavage of acetal or ester bonds, allowing the recovery of structures terminated with aldehyde/hydroxyl end groups or PBT. Both recycled products could be repolymerized. Overall, HT is an effective biobased precursor that can prepare PBT-based copolyesters with excellent physical properties and dual closed-loop recyclability.

Organic luminescent materials are essential for OLEDs and bioimaging, yet traditional π-conjugated molecules face synthetic and environmental challenges. Nonconventional luminescent materials (NLMs) offer better biocompatibility but typically exhibit weak clustering-triggered emission (CTE) in dilute solutions, limiting their biomedical utility. To address this, we synthesized four aspartic acid-based NLMs (S1-S4) featuring hydrophobic segments. These polymers self-assemble into nanoclusters in dilute solutions, restricting molecular motion to enable potent CTE. Remarkably, S1-S4 achieved high photoluminescence quantum yields (up to 10.07% at 0.5 mg/mL) and demonstrated low cytotoxicity. These NLMs function as effective lipid droplet (LD) imaging agents; specifically, S4 exhibited a 94% colocalization rate with the commercial probe Nile Red. By achieving performance comparable to traditional fluorescent probes in dilute states, these NLMs provide a robust, sustainable tool for specific subcellular imaging and advance the practical application of nonconjugated emitters.