Biomacromolecules最新文献

Computationally designed homotetrameric helical peptide bundles have been functionalized at their N-termini to achieve supramolecular polymers, wherein individual bundles ("bundlemers") are the monomeric units. Adjacent bundles are linked via two covalent cross-links. The polymers exhibit a range of conformational properties, including formation of rigid-rods with micrometer-scale persistence lengths. Herein, a coarse-grained model is used to illuminate how molecular features affect the rod-like behavior of the polymers. With increasing affinity between bundlemer ends, a sharp transition in the persistence length is observed. Doubly linked chains exhibit larger persistence lengths and more robust formation of rigid-rod structures than singly linked chains. Chain stiffness increases with decreasing temperatures. Increasing the length of the cross-linker results in more flexible chains. This model provides insights into how molecular features control the structural properties of chains comprising doubly linked rigid bundlemers.

Fusion of intrinsically disordered and globular proteins is a powerful strategy to create functional nanomaterials. However, the immutable nature of genetic encoding restricts the dynamic adaptability of nanostructures postexpression. To address this, we envisioned using a myristoyl switch, a protein that combines allostery and post-translational modifications─two strategies that modify protein properties without altering their sequence─to regulate intrinsically disordered protein (IDP)-driven nanoassembly. A typical myristoyl switch, allosterically activated by a stimulus, reveals a sequestered lipid for membrane association. We hypothesize that this conditional exposure of lipids can regulate the assembly of fusion proteins, a concept we term "liposwitching". We tested this by fusing recoverin, a calcium-dependent myristoyl switch, with elastin-like polypeptide, a thermoresponsive model IDP. Biophysical analyses confirmed recoverin's myristoyl-switch functionality, while dynamic light scattering and cryo-transmission electron microscopy showed distinct calcium- and lipidation-dependent phase separation and assembly. This study highlights liposwitching as a viable strategy for controlling DP-driven nanoassembly, enabling applications in synthetic biology and cellular engineering.

This study explored the potential of rose aqueous extract (RE), a byproduct of rose essential oil extraction, to enhance the properties of biobased food packaging materials. RE contained a high phenolic content (153 mg of GAE/g of dw), rich in hydroxybenzoic acids and flavonols. The antioxidant potential of RE, assessed by DPPH assay, was evaluated (IC₅₀ = 2.85 μg/mL). Edible pectin films fortified with RE were prepared, and their mechanical, physical, and chemical characteristics were evaluated. RE addition increased the moisture content from 14 to 28%, while moisture uptake remained stable at around 10%. Zeta potential remained below -30 mV, indicating that particle aggregation and particle size decreased with higher RE concentrations. Scanning electron microscopy showed an improved homogeneity of the films. RE retained its antioxidant properties, enhancing the mechanical resistance of the films and offering protection against oxidative damage and UV radiation. These findings suggest the potential of RE in developing functional, eco-friendly food packaging.

Medical adhesives have been used under surgical conditions. However, it is always a big challenge to maintain long-term adhesion in a water environment. Besides, it usually takes a long time to complete the adhesion, and the operation might be complicated. In this study, tannic acid and gelatin solution under acidic conditions were mixed, flocculated, lyophilized, and crushed; thus, a powdered medical adhesive (POWDER) was prepared with long-lasting adhesion in a water environment, convenience, and low price. Tannic acid bound gelatin and maintained adhesive force primarily through hydrogen bonding and reacted with amino sulfhydryl and other amino acid residues after oxidation into aldehyde, exhibiting excellent underwater adhesion. Oxidized dextran (ODex) powder rich in an aldehyde group was introduced to provide covalent binding in the adhesive. In vitro and in vivo studies showed that POWDER could quickly adhere to various tissues in the water environment. In vitro skin adhesion experiments demonstrated that it could achieve effective adhesion in a water environment for up to 60 days. Its blood compatibility, low cytotoxicity, and biodegradability were also verified. The POWDER developed in this study is of great significance for patients who need rapid wound treatments.

Hyaluronic acid (HA) is a biomedically relevant polymer widely explored as a component of hydrogels. The prevailing approaches for cross-linking HA into hydrogels require chemically modifying the polymer, which can increase processing steps and complicate biocompatibility. Herein, we demonstrate an alternative approach to cross-link HA that eliminates the need for chemical modifications by leveraging the interactions between metal cations and the negatively charged, ionizable functional groups on HA. We demonstrate that HA can be cross-linked with the bivalent metal cations Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), and notably Mg(II). Using Mg(II) as a model, we show that ion-HA hydrogel rheological properties can be tuned by altering the HA molecular weight and concentrations of ions, NaOH, and HA. Mg(II)-HA hydrogels showed the potential for self-healing and stimulus response. Our findings lay the groundwork for developing a new class of HA-based hydrogels for use in biomedical applications and beyond.

Polyzwitterions that show the alternation of net charge in response to external stimuli have attracted great attention as a new class of surface-polymers on nanomedicines. However, the correlation between their detailed molecular structures and expression of antifouling properties under physiological condition remain controversial. Herein, we synthesized a series of ethylenediamine-based polyzwitterions with carboxy groups/sulfonic groups and ethylene, propylene, and butylene spacers as potential surface-polymers for nanomedicines, allowing sensitive recognition of tumor acidic environments (pH = 6.5-5.5). Then, we evaluated their structure-based characteristics, including pH-dependent cellular uptakes and intracellular distributions. Additionally, the role of conformation stability, i.e., Gibbs free energy changes, was to induce an intramolecular electrostatic interaction in the zwitterionic moieties. These results highlight the practicality of fine-tuning the design of zwitterionic moieties on polymers for the future development of nanomedicines that can recognize the narrow pH window in tumor acidic environments.

Zwitterionic polymers have been found to be biocompatible alternatives to poly(ethylene glycol) (PEG) for conjugation to proteins. This work reports the site-selective conjugation of poly(caprolactone-carboxybetaine) (pCLZ) to human growth hormone receptor antagonist (GHA) B2036-alkyne and investigation of safety, activity, and pharmacokinetics. Azide-end-functionalized pCLZs were synthesized and conjugated to GHA B2036-alkyne via copper-catalyzed click reaction. The resulting inhibitory bioactivity concentration responses in Ba/F3-GHR cells were compared to those of PEGylated GHA B2036. IgG and IgM antibody production was tested in mice, and no measurable antibody or cytokine production was detected for the pCLZ conjugate. Using ¹⁸F-labeled PET/CT imaging, the pCLZ conjugate showed an increase in circulation time compared to that of GHA B2036. Acute toxicity of the polymer was investigated in vivo and found to be nontoxic. Ex vivo degradation of the polymer on the conjugate was investigated. The results suggest that pCLZ-GHA is a potentially safe alternative to PEG-GHA.

In situ polymerization on cell membranes can decrease cell mobility, which may inhibit tumor growth and invasion. However, the initiation of radical polymerization traditionally requires exogenous catalysts or free radical initiators, which might cause side effects in normal tissues. Herein, we synthesized a Y-type diacetylene-containing lipidated peptide amphiphile (TCDA-KFFFFK(GRGDS)-YIGSR, Y-DLPA) targeting integrins and laminin receptors on murine mammary carcinoma 4T1 cells, which underwent nanoparticle-to-nanofiber morphological transformation and in situ polymerization on cell membranes. Specifically, the polymerized Y-DLPA induced 4T1 cell apoptosis and disturbed the substance exchange and metabolism. In vitro assays demonstrated that the polymerized Y-DLPA nanofibers decreased the migration capacity of 4T1 cells, potentially suppressing tumor invasion and metastasis. When administered locally to 4T1 tumor-bearing mice, the Y-DLPA nanoparticles formed a biomimetic extracellular matrix that effectively suppressed tumor growth. This study provides an in situ polymerization strategy that can serve as an effective drug-free biomaterial with low side effects for antitumor therapy.

Proteins derived from agroindustrial coproducts and a natural cross-linking agent (genipap oil containing genipin) were used to develop porous materials by reactive extrusion for replacing fossil-based absorbents. Incorporating genipap oil allowed the production of lightweight structures with high saline uptake (above 1000%) and competing retention capacity despite their porous nature. The mechanical response of the genipap-cross-linked materials was superior to that of the noncross-linked ones and comparable to those cross-linked using commercial genipin. The extruded products were hemocompatible and soil-biodegradable in less than 6 weeks. The compounds generated by the degradation process were not found to be toxic to the soil, showing a high bioassimilation capacity by promoting grass growth. The results demonstrate the potential of biopolymers and new green cross-linkers to produce fully renewable-based superabsorbents in hygiene products with low ecotoxicity. The study further promotes the production of these absorbents using low-cost proteins and continuous processing such as reactive extrusion.