Biomacromolecules
· 2026 Jun · PMID 42358192
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Triple-negative breast cancer (TNBC) remains one of the most aggressive breast cancer subtypes with insufficient therapeutic opportunities and poor clinical outcomes. This challenge can be addressed to a great extent by...Triple-negative breast cancer (TNBC) remains one of the most aggressive breast cancer subtypes with insufficient therapeutic opportunities and poor clinical outcomes. This challenge can be addressed to a great extent by immunotherapy, but its clinical efficacy is substantially limited by the immunosuppressive tumor microenvironment. To overcome these barriers, an intelligent M1-type macrophage membrane camouflaged biomimetic nanoplatform based on cholesterol-functionalized glycopolymers bearing a photodynamic therapy (PDT)-active unit protoporphyrin IX (PpIX) and pH-responsive linkages for doxorubicin (Dox) conjugation has been developed to suppress TNBC through the combination of chemo-photodynamic therapy and immune remodeling. The therapeutic efficacy of the NP-Dox@M1 nanoplatform against metastatic TNBC was systematically evaluated in vitro through a comparative analysis of membrane-coated (NP@M1) versus uncoated (NP) constructs and drug-loaded (NP-Dox) versus drug-free formulations under conditions with or without light irradiation. The NP-Dox@M1 nanoplatform enables the synergistic combination of enhanced chemo-photodynamic therapy and immune regulation by promoting the polarization of macrophages toward an M1-like phenotype and reducing macrophage uptake, demonstrating potential immune evasion for the effective treatment of TNBC.
Liu P, Zou D, Chen C
… +6 more, Zhang W, Ding X, Tang N, Li H, Gao L, Yu Y
Biomacromolecules
· 2026 Jun · PMID 42350358
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Hydrogel adhesives that simultaneously possess high toughness, strong interfacial adhesion, and freeze resistance are urgently needed for emerging flexible electronics and wearable devices. However, conventional hydrogel...Hydrogel adhesives that simultaneously possess high toughness, strong interfacial adhesion, and freeze resistance are urgently needed for emerging flexible electronics and wearable devices. However, conventional hydrogels typically suffer from weak bonding to diverse substrates and brittle failure under subzero conditions. Herein, we present a cation-dipole-enhanced eutectic organohydrogel (APQ-DES) constructed via an interpenetrating network strategy using a choline chloride/glycerol deep eutectic solvent (DES) as the dispersion medium. The system combines chemically cross-linked polyacrylamide (PAM), poly(vinyl alcohol) (PVA), and cationic quaternary ammonium chitosan (QCS). The DES endows the hydrogel with excellent freeze tolerance, while synergistic cation-dipole interactions between QCS and various substrates, together with hydrogen bonding from PVA and PAM, enable robust adhesion across diverse materials, including PTFE, rubber, glass, and wood, achieving lap-shear strengths up to 584.57 kPa. The optimized APQ-DES hydrogel exhibits outstanding mechanical properties (tensile strength: 206.99 kPa, elongation at break: 1891%, toughness: 1.71 MJ·m), maintains flexibility and ionic conductivity at -20 °C, and functions as a reliable strain sensor with rapid response (361 ms), broad sensing range (0-400% strain), and stable cyclic performance. Demonstrations of multisite human motion monitoring under cold conditions highlight its potential for winter sports training evaluation, human-machine interfaces, and low-temperature wearable healthcare applications.
Fu C, Liu G, Wang J
… +3 more, Fan Y, Wei G, Xiao J
Biomacromolecules
· 2026 Jun · PMID 42350307
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Collagen-based bioinks are highly desirable for regenerative biofabrication owing to their intrinsic bioactivity and native triple-helical structure; however, their application in light-based bioprinting is severely cons...Collagen-based bioinks are highly desirable for regenerative biofabrication owing to their intrinsic bioactivity and native triple-helical structure; however, their application in light-based bioprinting is severely constrained by poor solubility, limited photocurability, and incompatibility with direct cell delivery under physiological conditions. Here, we report a one-step, cell-ready itaconylated collagen (CIA) bioink that enables visible-light digital light processing (DLP) bioprinting at neutral pH. CIA dissolves readily in aqueous media to form transparent precursor solutions suitable for rapid photo-crosslinking and high-fidelity fabrication. Compared with collagen methacrylate (CMA), CIA exhibits superior solubility, printability, and cytocompatibility while preserving collagen biofunctionality. CIA supports direct encapsulation of multiple cell types with high viability and enables fabrication of well-defined porous constructs. In a diabetic wound model, CIA hydrogels accelerated wound closure, reduced inflammation, enhanced angiogenesis, and promoted tissue remodeling. These findings establish CIA as a practical collagen bioink for cell-enabled DLP bioprinting and regenerative wound repair.
Biomacromolecules
· 2026 Jun · PMID 42347970
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The predominance of Aβ42 fibrils in parenchymal plaques of Alzheimer's disease (AD), despite the higher abundance of Aβ40 capable of coaggregation with Aβ42, remains an open question of the disease. We postulate that the...The predominance of Aβ42 fibrils in parenchymal plaques of Alzheimer's disease (AD), despite the higher abundance of Aβ40 capable of coaggregation with Aβ42, remains an open question of the disease. We postulate that the molecular chaperone Bri2 BRICHOS, an endogenous substoichiometric inhibitor of Aβ aggregation, may contribute to this mystery. Using atomistic replica-permutation discrete molecular dynamics simulations, we investigated the modulatory effects of BRICHOS on the fibril growth of both Aβ42 and Aβ40 by comparing their self- and cross-seeding processes. Aβ42 fibrils exhibited a higher fibrillization rate and greater thermal stability than Aβ40 fibrils, consistent with their higher amyloidogenicity. Both Aβ42 and Aβ40 fibrils were capable of efficiently cross-seeding the aggregation of the other variant, with fibril growth pathways determined by the seed morphology rather than the type of incoming monomer. However, BRICHOS showed a pronounced competitive advantage over Aβ40 monomer for binding Aβ40 fibril, thereby effectively capping the growth of Aβ40. The same effect, albeit much weaker, was also observed for Aβ42 fibrillization. This differential inhibition provides a possible mechanistic explanation for the scarcity of Aβ40 in fibrillar form in the AD brain despite its greater abundance and capability for cross-aggregation. Our findings highlight the combined influence of intrinsic fibril properties and selective environmental modulators in shaping amyloid deposit composition, providing new insights into AD pathogenesis and potential therapeutic strategies.
Chen J, Chen L, Shi H
… +8 more, Hu J, Wang Y, Gong M, Xu P, Yu P, Wang Y, Hu Z, Zeng Z
Biomacromolecules
· 2026 Jun · PMID 42345334
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Atopic dermatitis (AD) is a chronic inflammatory skin disease whose treatment is limited by side effects and poor drug stability. Dihydromyricetin (DHM) shows promise in alleviating skin inflammation, yet effective local...Atopic dermatitis (AD) is a chronic inflammatory skin disease whose treatment is limited by side effects and poor drug stability. Dihydromyricetin (DHM) shows promise in alleviating skin inflammation, yet effective localized and sustained delivery remains challenging. Herein, a β-lactoglobulin-based dual-network (BDN) hydrogel was developed by exploiting the structural plasticity of β-lactoglobulin monomers (BLGMs) to construct two distinct β-lactoglobulin-based (BLG-based) polymers, with DHM incorporated to obtain the BDN-DHM hydrogel. Photo-cross-linkable glycidyl methacrylate-modified β-lactoglobulin (BLG-GMA) polymers formed an irreversible covalent network, while β-lactoglobulin fibrils (BLGFs) established a dynamic network through Schiff-base reactions with oxidized dextran (ODEX). The resulting BDN-DHM hydrogel exhibited high mechanical strength, sustained drug release, antioxidant activity, and anti-inflammatory effects. studies further showed alleviation of AD-like symptoms and enhanced skin repair. Overall, the outcomes demonstrate the BDN-DHM hydrogel as a promising local dressing for AD and underscore the potential of BLGMs as versatile building blocks for multifunctional biomaterials.
Biomacromolecules
· 2026 Jun · PMID 42341145
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Articular cartilage (AC) defects can lead to joint destruction and osteoarthritis, necessitating immediate intervention to prevent progressive cartilage degeneration. To support cartilage repair, hydrogels have been expl...Articular cartilage (AC) defects can lead to joint destruction and osteoarthritis, necessitating immediate intervention to prevent progressive cartilage degeneration. To support cartilage repair, hydrogels have been explored due to their structural similarity to the extracellular matrix (ECM), offering a hydrated microenvironment for chondrocytes that promotes cell adhesion and proliferation. Polyurethane (PU) is a promising candidate with adjustable mechanical properties, high biocompatibility, and degradability. Given the advantages of both hydrogels and PU for biomedical applications, functional degradable PU hydrogels present a potential solution for cartilage regeneration. This review summarizes the structure-property relationship and degradation mechanisms of PU hydrogels. Their advanced functionalities in cartilage repair are highlighted, including anti-inflammatory and antibacterial properties, controlled drug delivery, injectability, self-healing, and stimulus responsiveness. By reviewing recent advances and emerging technologies, this review provides valuable insights and a future outlook for the development of next-generation cartilage repair materials.
LaFrance HM, Chea JD, Kinaci E
… +3 more, Howard KD, Newell JA, Stanzione JF
Biomacromolecules
· 2026 Jun · PMID 42338174
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Birch bark, often discarded or burned as a low-grade fuel in the pulp and paper industry, contains valuable compounds with significant potential as biobased polymer precursors. Among these are triterpenoids such as betul...Birch bark, often discarded or burned as a low-grade fuel in the pulp and paper industry, contains valuable compounds with significant potential as biobased polymer precursors. Among these are triterpenoids such as betulin, betulinic acid, and lupeol, which comprise roughly 10-40% of the dried bark mass, alongside lignocellulosic and suberin fractions. In this work, crude birch bark extract (BBE) was extracted and used directly as a polymer precursor material. Epoxidized BBE was cured with a range of biobased and petroleum-derived amines, including furan-derived difuran diamine (DFDA). The resulting thermoset polymers demonstrated high extents of cure (greater than 99%) and room-temperature storage moduli, glass transition temperatures, and thermal stabilities comparable to those of petroleum-derived epoxy systems.
Wang WH, Wu YC, Hung HM
… +4 more, Wang KC, Senthilkumar D, Hung YC, Kuo CY
Biomacromolecules
· 2026 Jun · PMID 42331784
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A new class of triple-staged, thermosensitive hydrogels has been developed using double cross-linking between succinyl chitosan (SC) and poly(-isopropylacrylamide--5-methacrylamido-1,2-benzoxaborole) and poly(NIPAM--MAAm...A new class of triple-staged, thermosensitive hydrogels has been developed using double cross-linking between succinyl chitosan (SC) and poly(-isopropylacrylamide--5-methacrylamido-1,2-benzoxaborole) and poly(NIPAM--MAAmBO) copolymers. Poly(NIPAM--MAAmBO) was first synthesized via RAFT polymerization with various monomer ratios and cross-linked by the hydroxyl groups on chitosan with poly(MAAmBO) segments to form the boronate ester bonding. Combining with the thermoresponsive poly(NIPAM) segments, we successfully prepared a dual-cross-linked hydrogel demonstrating a unique triple-staged, temperature-induced, sol-gel-sol transition behavior. This hydrogel exhibits injectability and self-healing capabilities. The mechanical properties of hydrogels can be tuned by adjusting the copolymer structure, hydrogel composition, temperature, and pH conditions. Among the various formulations, the hydrogel with a composition of SC/poly(NIPAM--MAAmBO) = 5/5 (w/w) exhibited superior mechanical properties, with a storage modulus (') of approximately 1000 Pa at pH 7.4 and 37 °C. Rheological analysis confirmed the stability, pH responsiveness, and reversible temperature-induced sol-gel-sol transitions of the hydrogel. In summary, we demonstrated that the microstructure and properties of the SC/poly(NIPAM--MAAmBO) hydrogels could be tailored through dynamic boronate ester bonds and temperature-responsive hydrogen bonds, showcasing significant potential for biomedical applications.
Biomacromolecules
· 2026 Jun · PMID 42329857
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Functionalized microspheres made from various materials are widely used for multiple biotechnological purposes. Proteins and peptides are commonly used for microsphere functionalization to leverage their biological funct...Functionalized microspheres made from various materials are widely used for multiple biotechnological purposes. Proteins and peptides are commonly used for microsphere functionalization to leverage their biological functions. However, the function of many proteins is modulated by plasma or organelle membranes; despite this, there is a scarcity of functionalized membrane-coated microspheres for applications that benefit from the presence of membranes. Here, we describe a simple and versatile method to functionalize microspheres of different sizes and materials with a synthetic membrane carrying integrated peptides designed for bioconjugation with other peptides and fully folded proteins. We have validated our method by producing membrane-coated microspheres functionalized with a fluorescent peptide and a DNA-binding protein. Using confocal fluorescence microscopy and optical traps, we demonstrate these functions and the possibility of measuring mechanical forces associated with protein-DNA binding. In addition, we have determined microsphere labeling efficiencies close to 100% by flow cytometry. Our results open the door to the fabrication of multifunctionalized membrane-coated microspheres for an ample range of purposes, and specifically, the study and leverage of protein function that requires or is enhanced by the presence of a lipid bilayer.
Wang X, Zhang T, Gong X
… +5 more, Wu Y, Zhao Z, Wang Z, Ding W, Wu Y
Biomacromolecules
· 2026 Jun · PMID 42329160
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Developing high-performance biopackaging is crucial for mitigating plastic pollution and advancing a sustainable circular economy. Guided by a supramolecular design strategy, this work presented a novel, mechanically str...Developing high-performance biopackaging is crucial for mitigating plastic pollution and advancing a sustainable circular economy. Guided by a supramolecular design strategy, this work presented a novel, mechanically strong, and bioactive gelatin-based composite plastic film constructed by sequentially incorporating carboxylated cellulose nanofibers (CCNF), gallic acid (GA), and Al, forming a multicross-linked network. The rigid CCNF phase drastically enhanced surface hydrophobicity (water contact angle: 113.9°). GA incorporation achieved near-complete DPPH/ABTS free radical scavenging (∼100%), validated by practical blueberry preservation, and increased elongation at break by 384%, indicating a brittle-to-ductile transition. Subsequent Al coordination further strengthened the composite film, yielding a tensile strength of 28.7 MPa and a Young's modulus of 828 MPa. The final multicross-linked film (GCGAF) exhibited excellent thermal stability, robust gas barrier properties, notable antibacterial activity, and favorable biodegradability. This work provides an effective strategy for fabricating high-performance gelatin-based supramolecular plastics with balanced and superior properties for practical packaging applications.
Venrooij KR, van Weijsten MJ, Kroos S
… +6 more, Hammink R, Turlings F, Figdor CG, Verdoes M, Toes REM, Bonger KM
Biomacromolecules
· 2026 Jun · PMID 42329059
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Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic inflammation and joint damage. Current treatments rely on systemic immune suppressors, which increases infection risk. Autoreactive...Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic inflammation and joint damage. Current treatments rely on systemic immune suppressors, which increases infection risk. Autoreactive B cells directed against citrullinated antigens and producing anticitrullinated protein antibodies (ACPAs) are thought to play a key role in RA pathogenesis, making their selective elimination a promising therapeutic strategy. Previous research demonstrated that a synthetic multivalent citrullinated antigen, cyclic citrullinated peptide 4 (CCP4), is efficiently internalized by these autoreactive B cells through an antigen-specific B cell receptor (BCR), positioning it as a potential delivery vehicle for targeted therapy. Here, we explored the elimination of autoreactive B cells using multivalent antigen-cleavable linker-toxin conjugates. Initial evaluation of diCCP4-VCP-MMAE revealed that it lacked sufficient toxicity toward ACPA BCR-expressing Ramos cells despite cathepsin-mediated linker cleavage and the absence of steric hindrance from diCCP4 or the BCR. Therefore, we investigated polyisocyano peptide (PIC) polymers, which allow for a higher CCP4 and toxin density. PIC 13 (containing 13 CCP4 units), functionalized with 0.5 equiv of MMAE per CCP4, selectively eliminated Ramos 3F3 cells with a midnanomolar IC. Increasing MMAE to 1, 2, or 5 equiv further reduced the IC to low nanomolar. PIC 13 + 5 equiv MMAE demonstrated selective toxicity in Ramos cells expressing various ACPA BCRs, as well as patient-derived, immortalized ACPA-expressing B cells. These findings underscore the importance of optimizing delivery modules and toxin ratios and highlight PIC-based antigen-toxin conjugates as a promising strategy for selectively eliminating autoreactive B cells in RA.
Biomacromolecules
· 2026 Jun · PMID 42325055
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Biofouling poses major challenges in marine and biomedical sectors. To overcome the substrate-specific limitations of conventional poly(ethylene glycol) (PEG) coatings, we report herein a versatile, mussel-inspired ancho...Biofouling poses major challenges in marine and biomedical sectors. To overcome the substrate-specific limitations of conventional poly(ethylene glycol) (PEG) coatings, we report herein a versatile, mussel-inspired anchoring strategy. Using catechol-amine functionalized copolyethers, we created substrate-independent antifouling PEG brushes. To elucidate the synergistic role of catechol and amine groups, three control copolymers (catechol-only, phenol-amine, and phenyl-amine) were synthesized via anionic ring-opening polymerization using a PEG macroinitiator. Comprehensive characterization revealed that catechol-amine synergy achieved the highest grafting density (0.82 chains/nm) and superior antifouling efficacy. Notably, the phenol-amine variant showed higher grafting density than the phenyl-amine control but significantly worse antifouling performance. Suboptimal anchoring leaves exposed chemical motifs that inadvertently promote biofouling. This demonstrates that high grafting density alone cannot guarantee fouling resistance; the chemical integrity of the anchoring moiety is decisive. These findings underscore the catechol-amine platform as a critical requirement for high-performance, robust antifouling interfaces.
Sun M, Lv R, Sha Y
… +4 more, Zhu L, Cao J, Zhong Z, Meng F
Biomacromolecules
· 2026 Jun · PMID 42322270
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Inflammatory bowel disease (IBD) is a relapsing gastrointestinal disorder depicted by persistent oxidative/nitrosative stress, mucosal barrier disruption, and maladaptive immune activation. Herein, we report that sulfasa...Inflammatory bowel disease (IBD) is a relapsing gastrointestinal disorder depicted by persistent oxidative/nitrosative stress, mucosal barrier disruption, and maladaptive immune activation. Herein, we report that sulfasalazine- and cerium ion-loaded polymersomes (SSZ/Ce-Some) that effectively treat IBD through superior capability of scavenging reactive oxygen and nitrogen species (RONS) and promotion of colonic mucosal repair. SSZ/Ce-Some exhibits potent superoxide dismutase (SOD)-like and catalase (CAT)-like catalytic activities, efficiently scavenges representative ROS, and markedly generates oxygen. Its excellent neutralization of RNS (NO) together with superoxide indicates inhibition of tissue-destructive peroxynitrite. SSZ/Ce-Some inhibits inflammatory macrophages and dendritic cell activation and suppresses pro-inflammatory cytokine secretion. In acute colitis, SSZ/Ce-Some accumulates in inflamed colons, alleviates intestinal inflammation, and preserves epithelial tight junction integrity. Moreover, oral SSZ/Ce-Some in a mucoadhesive hydrogel safely and effectively treats chronic Crohn's disease, with tissue repair and immune regulation. Overall, SSZ/Ce-Some with superior RONS-detoxifying capacity represents a promising therapeutic strategy for IBD treatment.
Yang Y, Wang S, Ma Y
… +4 more, Yang D, Li X, Li X, Che H
Biomacromolecules
· 2026 Jun · PMID 42322008
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Enzyme-enabled biocatalysis demonstrates potent reactive oxygen species (ROS) scavenging performance for oxidative stress mitigation. However, the intrinsic stability and catalytic activity of enzymes are highly suscepti...Enzyme-enabled biocatalysis demonstrates potent reactive oxygen species (ROS) scavenging performance for oxidative stress mitigation. However, the intrinsic stability and catalytic activity of enzymes are highly susceptible to harsh external microenvironments, which severely restricts their potential applications. Herein, we report the rational design of oxidation-responsive polymeric nanoreactors through encapsulating enzymes within self-assembled vesicular architectures, namely, polymersomes. Upon stimulation with ROS, the membrane permeability of the polymersomes is substantially enhanced, thereby triggering the activation of the encapsulated superoxide dismutase (SOD) and catalase (CAT). Specifically, SOD efficiently scavenges superoxide anions (•O) while CAT catalyzes the decomposition of HO, enabling sequential and synergistic ROS elimination. Both in vitro and in vivo assessments demonstrate that these oxidation-responsive polymersome nanoreactors significantly improve the therapeutic outcomes for osteoarthritis (OA), offering a versatile and biocompatible platform for the treatment of inflammation-related diseases.
Mueller E, Garza Flores NA, Mirzaie S
… +7 more, Yin R, Fredenburgh JC, Lopes H, Zhou ZF, Weitz JI, Wu XY, Hoare T
Biomacromolecules
· 2026 Jun · PMID 42319790
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Zwitterionic polymers such as poly(sulfobetaines) and polyether polymers such as poly(ethylene glycol) (PEG) have both been reported as effective antifouling materials for various biomedical applications based on their h...Zwitterionic polymers such as poly(sulfobetaines) and polyether polymers such as poly(ethylene glycol) (PEG) have both been reported as effective antifouling materials for various biomedical applications based on their high-water-binding capacities through hydrogen bonding (PEG) or ion-dipole interactions (zwitterionic polymers). Herein, to assess whether synergistic antifouling properties can be achieved when poly(sulfobetaine) and PEG moieties are combined into a single polymer, linear copolymers were fabricated by the chain transfer radical copolymerization of [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (DMAPS) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) together with a functional comonomer that introduced an aldehyde or hydrazide functional group to enable in situ gelation via hydrazone cross-linking. In general, hydrogels prepared with more OEGMA showed longer gelation times, increased protein uptake (because of their higher degree of swelling), and faster plasma clotting times. However, hydrogels prepared with hydrazide precursor polymers with a 90:10 molar ratio of DMAPS:OEGMA exhibited significantly lower protein adsorption as well as lower peak thrombin upon exposure to blood plasma compared to either single-component gel. This result was rationalized by molecular dynamics simulations indicating that the 90:10 DMAPS:OEGMA ratio facilitates enhanced total hydration, a more dynamic hydration sphere, and suppressed zwitterion fusion interactions. Overall, the results suggest a potential benefit of introducing multiple types of water-binding mechanisms into a single antifouling biomaterial.
Chen C, Shan Z, Gu Y
… +7 more, Ding Y, Yang Y, Wu W, Jin Y, Manan S, Rahman MM, Jiang B
Biomacromolecules
· 2026 Jun · PMID 42319084
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The controlled-release hydrogel with dual-dynamic-bond networks provides superior tunability and stability through collaborative exchange mechanisms, which are often used for drug release. However, the impact of its mult...The controlled-release hydrogel with dual-dynamic-bond networks provides superior tunability and stability through collaborative exchange mechanisms, which are often used for drug release. However, the impact of its multiscale structures involving various orientations and cross-linking densities on release kinetics is still poorly understood. Herein, a dual-dynamic-bond cross-linked hydrogel with tunable structures (orientation and cross-linking density) was developed, where the cross-linked network is formed by imine bonds between aminated lignin and oxidized carboxymethyl cellulose, as well as borate ester bonds between 3-aminophenylboronic acid-grafted sodium alginate and epigallocatechin gallate (EGCG). The results showed that the imine/borate ester cross-linked dual-network hydrogel exhibits pronounced pH responsiveness, enabling synergistic release of lignin and EGCG. Compared with the isotropic structures, the anisotropic hydrogel shows significantly faster release for lignin and EGCG along the aligned microchannels, which is attributed to the shortened mass-transfer pathways. In addition, driven by the stronger interfacial interaction of polar groups, the denser network attributed to the increased freeze-thaw cycles further accelerates the co-release of lignin and EGCG. The release process follows a non-Fickian diffusion mechanism and can be well described by the Korsmeyer-Peppas model. This work establishes a direct structure-release kinetics correlation, paving the way for the design of a dual-dynamic-bond hydrogel for precision delivery.
Agarwal V, Saini V, Prasun A
… +4 more, Varshney N, Chakraborty A, Jha HC, Sarma TK
Biomacromolecules
· 2026 Jun · PMID 42318702
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Small peptides exhibit remarkable antimicrobial and biological functions, yet their translation into biomaterials often requires chemical modifications that can compromise their native functionalities. Physically cross-l...Small peptides exhibit remarkable antimicrobial and biological functions, yet their translation into biomaterials often requires chemical modifications that can compromise their native functionalities. Physically cross-linked hydrogels involving noncovalent interactions can retain pristine biomolecules, enabling their functional integration. Here, we present a facile strategy for constructing all-biomolecular hydrogels through the noncovalent integration of glutathione and guanosine monophosphate. The spontaneous formation of transparent, robust, and physically cross-linked hydrogels occurs via G-quadruplex assembly, preserving inherent biomolecular functionality. These hydrogels demonstrate good mechanical strength, broad pH stability, and self-healing behavior. Morphological analysis reveals protocell-like spherical intermediates, eventually yielding helical fibrillar networks. The supramolecular fibers exhibit dose-dependent cytocompatibility with selective bioactivities, suitable for biomedical applications. In vitro studies confirmed pronounced antiviral efficacy against Epstein-Barr virus and SARS-CoV-2, alongside broad-spectrum antibacterial efficacy. Additionally, the fibers induced apoptosis in gastric cancer cells. The viscoelastic and shape-sustaining behavior of these hydrogels holds potential scope to develop antimicrobial coating materials.
Biomacromolecules
· 2026 Jun · PMID 42317000
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Protein-polymer conjugation and microbial surface display are two dominant strategies for enzyme engineering, yet they have evolved in isolation, restricted by distinct limitations in purification or stability. Here, we...Protein-polymer conjugation and microbial surface display are two dominant strategies for enzyme engineering, yet they have evolved in isolation, restricted by distinct limitations in purification or stability. Here, we bridge this divide by introducing "grafted-from surface display," a platform that enables in situ atom transfer radical polymerization (ATRP) directly on surface-displayed proteins without prior and post purification. Using displaying a cysteine-engineered benzaldehyde lyase (sBAL), we grew thermoresponsive poly(-isopropylacrylamide) (PNIPAM) polymers that significantly enhanced the surface-displayed enzyme's robustness, retaining >60% activity at 50 °C where unmodified variants lost substantial function. This architecture preserves cell viability and allows for the reversible, temperature-controlled recovery and purification of membrane-bound biocatalysts via simple centrifugation. In a multienzyme cascade with alcohol dehydrogenase, the conjugates achieved a benzoin yield of 15 mM and retained over 80% activity after four recycling cycles. This strategy establishes a facile framework for integrating synthetic polymer chemistry with cellular machinery, creating robust, self-recovering biocatalysts while eliminating the need for laborious protein isolation.
Roychowdhury S, Menon S, Mandal N
… +3 more, Majumder S, Mondal J, Chattopadhyay K
Biomacromolecules
· 2026 Jun · PMID 42316432
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Intrinsically disordered regions (IDRs) from larger proteins are known to undergo liquid-liquid phase separation (LLPS) to form biomolecular condensates. This process is influenced by the conformational flexibility of th...Intrinsically disordered regions (IDRs) from larger proteins are known to undergo liquid-liquid phase separation (LLPS) to form biomolecular condensates. This process is influenced by the conformational flexibility of the protein and the crowded intracellular environment. Although several studies exist involving crowding agents to induce LLPS, the molecular understanding of crowding in phase separation has not been explored well. Herein, we investigate how molecular crowding, specifically the size and shape of crowders like Dextran and Ficoll, modulates the conformational states and phase separation behavior of Sup35NM, a disordered region of the yeast prion protein, Sup35. Using fluorescence correlation spectroscopy (FCS) and molecular dynamics simulations, we show that Dextran, depending on its molecular weight, induces both compaction and expansion of Sup35NM, driving phase separation beyond a particular threshold. Notably, flexible rod-like Dextran crowders promotes phase separation, while spherical Ficoll does not, highlighting the impact of crowder geometry on IDP behavior. Molecular simulation further revealed that the crowder shape influences Sup35NM's conformational ensemble by modulating intra- and inter-domain interactions. These findings elucidate the role of crowding agents in IDP phase behavior, suggesting that cellular crowding may regulate IDP functionality through conformational control.