Biomacromolecules最新文献

{"title":"Optimization of Affibody Affinity to Improve Distribution in Tumor Models","authors":"Bryce M. Bower,&nbsp;Gabrielle M. Ho,&nbsp;Sven A. Saemundsson,&nbsp;Andrew P. Goodwin,&nbsp;Jennifer N. Cha","doi":"10.1021/acs.biomac.6c01111","DOIUrl":"10.1021/acs.biomac.6c01111","url":null,"abstract":"<div><div>Poor distribution is often a limiting factor when using affinity targeted treatments. High affinity creates a barrier to transport because proteins cannot diffuse throughout the tissue while bound to the cell surface. Lowering the affinity can help with transport throughout a tumor but can also result in a loss of total delivery and specificity for the target. In this research, we used point mutations to create affibodies with a range of different affinities for epidermal growth factor receptor (EGFR) and measured their penetration through tumor spheroids. Mutants in the range of ∼7–12 nM <em>K</em> _D were able to distribute more evenly throughout 3D tumor spheroids without losing total accumulation or receptor specificity. Lower affinity mutants showed both low target specificity and accumulation in 3D tumor spheroids. This work shows the effects of affinity on distribution and how slightly reducing binding affinity can improve transport.</div></div><div>Poor distribution is often a limiting factor when using affinity targeted treatments. High affinity creates a barrier to transport because proteins cannot diffuse throughout the tissue while bound to the cell surface. Lowering the affinity can help with transport throughout a tumor but can also result in a loss of total delivery and specificity for the target. In this research, we used point mutations to create affibodies with a range of different affinities for epidermal growth factor receptor (EGFR) and measured their penetration through tumor spheroids. Mutants in the range of ∼7–12 nM <em>K</em> _D were able to distribute more evenly throughout 3D tumor spheroids without losing total accumulation or receptor specificity. Lower affinity mutants showed both low target specificity and accumulation in 3D tumor spheroids. This work shows the effects of affinity on distribution and how slightly reducing binding affinity can improve transport.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (52KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (52KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6134-6142"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust Silk Fibroin Aerogel Fibers Designed by Dual Cross-Linking for Thermal Insulation","authors":"Qianqian Niu,&nbsp;Xianghua Li,&nbsp;Yaopeng Zhang","doi":"10.1021/acs.biomac.6c01321","DOIUrl":"10.1021/acs.biomac.6c01321","url":null,"abstract":"<div><div>Silk fibroin (SF) is ideal for aerogel fibers owing to its abundance, biodegradability, biocompatibility, and structural tunability, yet pristine SF aerogel fibers have insufficient performance for practical use. Here, a dual cross-linking strategy combining enzymatic cross-linking and Zn²⁺ coordination was used, leveraging their noncompetitive inhibition to produce SF aerogel fibers featuring low density, high strength, and outstanding thermal insulation. SF concentration governs the pore architecture formed by enzymatic cross-linking. Zn²⁺ ions complex with SF molecular chains, creating a more intricate three-dimensional network alongside the covalent bonds from enzymatic cross-linking. At 0.1 M Zn²⁺, the dual-cross-linked SF aerogel fibers achieve a maximum toughness of ∼0.31 MJ m^–3 and optimal thermal insulation with ∼2.9 °C. Woven fabrics outperform commercial nylon, cotton and wool in thermal insulation. Superior performance arises from air-trapping pores suppressing conduction/convection and infrared-reflective pore walls reducing radiative loss. This work provides a guideline for designing biomass aerogel fibers.</div></div><div>Silk fibroin (SF) is ideal for aerogel fibers owing to its abundance, biodegradability, biocompatibility, and structural tunability, yet pristine SF aerogel fibers have insufficient performance for practical use. Here, a dual cross-linking strategy combining enzymatic cross-linking and Zn²⁺ coordination was used, leveraging their noncompetitive inhibition to produce SF aerogel fibers featuring low density, high strength, and outstanding thermal insulation. SF concentration governs the pore architecture formed by enzymatic cross-linking. Zn²⁺ ions complex with SF molecular chains, creating a more intricate three-dimensional network alongside the covalent bonds from enzymatic cross-linking. At 0.1 M Zn²⁺, the dual-cross-linked SF aerogel fibers achieve a maximum toughness of ∼0.31 MJ m^–3 and optimal thermal insulation with ∼2.9 °C. Woven fabrics outperform commercial nylon, cotton and wool in thermal insulation. Superior performance arises from air-trapping pores suppressing conduction/convection and infrared-reflective pore walls reducing radiative loss. This work provides a guideline for designing biomass aerogel fibers.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (147KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (147KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6227-6238"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Release of Antibiotics with Additive Effect from Cleavable Hydrogels Based on Amino/Thiol–Yne Click Chemistry","authors":"Sara Bescós-Ramo,&nbsp;Cristina Yus,&nbsp;Manuel Arruebo,&nbsp;Milagros Piñol,&nbsp;Luis Oriol","doi":"10.1021/acs.biomac.6c01230","DOIUrl":"10.1021/acs.biomac.6c01230","url":null,"abstract":"<div><div>Dual-antibiotic loaded poly­(ethylene glycol) (PEG)-based hydrogels were developed as antimicrobial wound dressings combining covalent and physical antibiotic incorporation. Hydrogels were prepared through amino-yne click conjugation of gentamicin sulfate (Gs) and thiol-yne cross-linking, followed by ciprofloxacin (CPX) loading via swelling-diffusion. The materials exhibited tunable gelation time, swelling capacity, and drug release profiles depending on thiol content. A dual-release mechanism was achieved, consisting of an initial burst release of CPX followed by a sustained, pH-responsive release of conjugated Gs through acid cleavage of β-aminoacrylate linkages. The hydrogels showed effective wide spectrum antibacterial activity against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, while cytotoxicity studies confirmed cytocompatibility at bactericidal concentrations. The results support the potential of these hydrogels as safe and effective dual-antibiotic wound dressings, allowing for the immediate elimination of invading bacteria after wounding (burst release), while maintaining long-term antibiotic release to minimize reinfection risk.</div></div><div>Dual-antibiotic loaded poly­(ethylene glycol) (PEG)-based hydrogels were developed as antimicrobial wound dressings combining covalent and physical antibiotic incorporation. Hydrogels were prepared through amino-yne click conjugation of gentamicin sulfate (Gs) and thiol-yne cross-linking, followed by ciprofloxacin (CPX) loading via swelling-diffusion. The materials exhibited tunable gelation time, swelling capacity, and drug release profiles depending on thiol content. A dual-release mechanism was achieved, consisting of an initial burst release of CPX followed by a sustained, pH-responsive release of conjugated Gs through acid cleavage of β-aminoacrylate linkages. The hydrogels showed effective wide spectrum antibacterial activity against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, while cytotoxicity studies confirmed cytocompatibility at bactericidal concentrations. The results support the potential of these hydrogels as safe and effective dual-antibiotic wound dressings, allowing for the immediate elimination of invading bacteria after wounding (burst release), while maintaining long-term antibiotic release to minimize reinfection risk.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (122KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (122KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6175-6189"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cutinase Adsorption to Polyester Surfaces Modulates Dissolved Oligomer Speciation during Enzymatic Depolymerization","authors":"Marc J. Foster,&nbsp;Parker J. McClain,&nbsp;Annabella S. Wardle,&nbsp;Natalie D. Mamrol,&nbsp;Elijah E. Martin,&nbsp;Glen Andrew D. de Vera,&nbsp;Bradley D. Olsen,&nbsp;Desirée L. Plata","doi":"10.1021/acs.biomac.6c00362","DOIUrl":"10.1021/acs.biomac.6c00362","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Surface-active enzymes, such as cutinases, initiate depolymerization of polyester plastics by adsorbing to the polymer surface. The influence of enzyme adsorption on the composition of dissolved degradation products remains underexplored. This study investigated how adsorption of a cutinase from Humicola insolens (HiC) to polyester surfaces modulated dissolved oligomer speciation during depolymerization of poly­(butylene succinate) (PBS) and poly­(butylene sebacate-co-terephthalate) (PBSeT). Inverse and conventional Michaelis–Menten kinetics were used to determine attack site densities (Γ&lt;sub&gt;attack&lt;/sub&gt;) and catalytic turnover (&lt;em&gt;k&lt;/em&gt; &lt;sub&gt;cat&lt;/sub&gt;). HiC exhibited comparable Γ&lt;sub&gt;attack&lt;/sub&gt; for PBS and PBSeT (0.31 ± 0.06 and 0.51 ± 0.12 μmol&lt;sub&gt;enzyme&lt;/sub&gt; g&lt;sub&gt;plastic&lt;/sub&gt; &lt;sup&gt;–1&lt;/sup&gt;, respectively), while the &lt;em&gt;k&lt;/em&gt; &lt;sub&gt;cat&lt;/sub&gt; was 2 orders of magnitude higher for PBS (40.8 ± 8.4 s&lt;sup&gt;–1&lt;/sup&gt; vs 0.13 ± 0.02 s&lt;sup&gt;–1&lt;/sup&gt;). Liquid chromatography coupled to mass spectrometry revealed accumulation of larger oligomers when the enzyme-to-plastic ratios were below the Γ&lt;sub&gt;attack&lt;/sub&gt;, indicating that relative free protein levels influence the composition of dissolved products during plastic depolymerization.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Surface-active enzymes, such as cutinases, initiate depolymerization of polyester plastics by adsorbing to the polymer surface. The influence of enzyme adsorption on the composition of dissolved degradation products remains underexplored. This study investigated how adsorption of a cutinase from Humicola insolens (HiC) to polyester surfaces modulated dissolved oligomer speciation during depolymerization of poly­(butylene succinate) (PBS) and poly­(butylene sebacate-co-terephthalate) (PBSeT). Inverse and conventional Michaelis–Menten kinetics were used to determine attack site densities (Γ&lt;sub&gt;attack&lt;/sub&gt;) and catalytic turnover (&lt;em&gt;k&lt;/em&gt; &lt;sub&gt;cat&lt;/sub&gt;). HiC exhibited comparable Γ&lt;sub&gt;attack&lt;/sub&gt; for PBS and PBSeT (0.31 ± 0.06 and 0.51 ± 0.12 μmol&lt;sub&gt;enzyme&lt;/sub&gt; g&lt;sub&gt;plastic&lt;/sub&gt; &lt;sup&gt;–1&lt;/sup&gt;, respectively), while the &lt;em&gt;k&lt;/em&gt; &lt;sub&gt;cat&lt;/sub&gt; was 2 orders of magnitude higher for PBS (40.8 ± 8.4 s&lt;sup&gt;–1&lt;/sup&gt; vs 0.13 ± 0.02 s&lt;sup&gt;–1&lt;/sup&gt;). Liquid chromatography coupled to mass spectrometry revealed accumulation of larger oligomers when the enzyme-to-plastic ratios were below the Γ&lt;sub&gt;attack&lt;/sub&gt;, indicating that relative free protein levels influence the composition of dissolved products during plastic depolymerization.&lt;/div&gt;&lt;div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (114KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download full-size image&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;/ol&gt;&lt;/span&gt;&lt;/figure&gt;&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;span&gt;&lt;figure&gt;&lt;span&gt;&lt;img&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download high-res image (114KB)&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;&lt;span&gt;Download: &lt;span&gt;Download full-size image&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/li&gt;&lt;/ol&gt;&lt;/s","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5908-5919"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective Reduction of Anti-PEG Antibody Recognition via PEG Copolymers with Ethyl Glycidyl Ether and Isopropyl Glycidyl Ether","authors":"Verena Müller,&nbsp;Julian Schmidt,&nbsp;Rebecca Matthes,&nbsp;Philip Dreier,&nbsp;Sandra Schüttner,&nbsp;Matthias Bros,&nbsp;Holger Frey","doi":"10.1021/acs.biomac.6c01182","DOIUrl":"10.1021/acs.biomac.6c01182","url":null,"abstract":"<div><div>Anti-PEG antibodies (APAs) lead to accelerated blood clearance of PEGylated drugs and nanocarriers. Randomized PEG (rPEG) reduces APA recognition by randomly incorporating glycidyl methyl ether in PEG. Extending this concept, statistical copolymerization of ethylene oxide with ethyl glycidyl ether (EGE) or isopropyl glycidyl ether (<em>i</em>PGE) was investigated. Copolymers of EO with 13–28 mol % EGE or 6–20 mol % <em>i</em>PGE showed low dispersity (<em>Đ</em> ≤ 1.09). Via online-NMR monitoring, reactivity ratios in DMSO were <em>r</em> _EO = 1.39 and <em>r</em> _EGE = 0.72 for P­(EO-<em>co</em>-EGE) and <em>r</em> _EO = 1.35 and <em>r</em> _{<em>i</em>PGE} = 0.74 for P­(EO-<em>co-i</em>PGE). All copolymers were soluble in PBS buffer at physiological temperatures and noncytotoxic, except for 20% <em>i</em>PGE content, shown by cell viability and immunostimulatory effects on murine splenocytes. All copolymers exhibit significantly reduced APA recognition (ELISA) with stronger effects for the sterically demanding <em>i</em>PGE. The findings highlight mP­(EO-<em>co</em>-EGE) and mP­(EO-<em>co-i</em>PGE) as promising PEG alternatives for nanomedicine and bioconjugation.</div></div><div>Anti-PEG antibodies (APAs) lead to accelerated blood clearance of PEGylated drugs and nanocarriers. Randomized PEG (rPEG) reduces APA recognition by randomly incorporating glycidyl methyl ether in PEG. Extending this concept, statistical copolymerization of ethylene oxide with ethyl glycidyl ether (EGE) or isopropyl glycidyl ether (<em>i</em>PGE) was investigated. Copolymers of EO with 13–28 mol % EGE or 6–20 mol % <em>i</em>PGE showed low dispersity (<em>Đ</em> ≤ 1.09). Via online-NMR monitoring, reactivity ratios in DMSO were <em>r</em> _EO = 1.39 and <em>r</em> _EGE = 0.72 for P­(EO-<em>co</em>-EGE) and <em>r</em> _EO = 1.35 and <em>r</em> _{<em>i</em>PGE} = 0.74 for P­(EO-<em>co-i</em>PGE). All copolymers were soluble in PBS buffer at physiological temperatures and noncytotoxic, except for 20% <em>i</em>PGE content, shown by cell viability and immunostimulatory effects on murine splenocytes. All copolymers exhibit significantly reduced APA recognition (ELISA) with stronger effects for the sterically demanding <em>i</em>PGE. The findings highlight mP­(EO-<em>co</em>-EGE) and mP­(EO-<em>co-i</em>PGE) as promising PEG alternatives for nanomedicine and bioconjugation.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (43KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (43KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6165-6174"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heavy Metal Chelation and Bioprotective Activity of Dextran-DOTA Macromolecular Conjugate","authors":"Sebastian Guajardo,&nbsp;Hunter Wood,&nbsp;Chenyun Deng,&nbsp;Neo Alpha,&nbsp;Stefanie A. Sydlik","doi":"10.1021/acs.biomac.6c00847","DOIUrl":"10.1021/acs.biomac.6c00847","url":null,"abstract":"<div><div>Widespread exposure and bioaccumulation of toxic heavy metals have increased the incidence of metal poisoning, particularly in children. Although chelation therapy can remove toxic metals, current drugs are limited by toxicity and side effects, restricting treatment to severe cases. We report the synthesis of a water-soluble macromolecular chelator through esterification of dextran with tetraxetan (DOTA) to create a safer systemic chelator. Chemical characterization confirmed successful conjugation with a high degree of substitution. The resulting Dex-DOTA conjugate exhibited enhanced affinity for lead and cadmium, demonstrating the advantages of macromolecular architecture for metal selectivity and retention. Dex-DOTA also showed excellent colloidal stability, no cytotoxicity, and improved cell survival following metal exposure. In C. elegans, the conjugate was nontoxic and mitigated heavy metal-induced toxicity. These findings establish Dex-DOTA as a stable, selective, and biocompatible chelator with strong potential for safer systemic treatment of heavy metal poisoning.</div></div><div>Widespread exposure and bioaccumulation of toxic heavy metals have increased the incidence of metal poisoning, particularly in children. Although chelation therapy can remove toxic metals, current drugs are limited by toxicity and side effects, restricting treatment to severe cases. We report the synthesis of a water-soluble macromolecular chelator through esterification of dextran with tetraxetan (DOTA) to create a safer systemic chelator. Chemical characterization confirmed successful conjugation with a high degree of substitution. The resulting Dex-DOTA conjugate exhibited enhanced affinity for lead and cadmium, demonstrating the advantages of macromolecular architecture for metal selectivity and retention. Dex-DOTA also showed excellent colloidal stability, no cytotoxicity, and improved cell survival following metal exposure. In C. elegans, the conjugate was nontoxic and mitigated heavy metal-induced toxicity. These findings establish Dex-DOTA as a stable, selective, and biocompatible chelator with strong potential for safer systemic treatment of heavy metal poisoning.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (125KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (125KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6009-6022"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elastin-Based Hydrogel for Selective Adsorption of Rare Earth Elements","authors":"Inseok Chae,&nbsp;Butaek Lim,&nbsp;Dylan S. Chang,&nbsp;Fiona M. Doyle,&nbsp;Seung-Wuk Lee","doi":"10.1021/acs.biomac.5c02269","DOIUrl":"10.1021/acs.biomac.5c02269","url":null,"abstract":"<div><div>The sustainable separation of rare earth elements (REEs) from complex mixtures remains a critical technological challenge. Biomaterials offer a promising route, but their deployment has been hindered by their limited stability and efficiency. Here, we report a robust elastin-based hydrogel incorporating the lanthanide-binding protein, lanmodulin, for efficient and selective REE separation. A fusion protein of elastin-like polypeptide and lanmodulin was synthesized and cross-linked with four-arm polyethylene glycol to form a porous network that enhances REE binding and release in aqueous environments. The protein-cross-linked hydrogel exhibits high internal selectivity for lanthanide ions over multiple regeneration cycles. When implemented as an ion exchange chromatography adsorbent, it enables the selective fractionation of lanthanides from allanite ore, a complex natural source containing abundant REEs and non-REEs. The combination of excellent selectivity and operational stability positions this protein hydrogel as a sustainable platform for eco-friendly REE separation and purification.</div></div><div>The sustainable separation of rare earth elements (REEs) from complex mixtures remains a critical technological challenge. Biomaterials offer a promising route, but their deployment has been hindered by their limited stability and efficiency. Here, we report a robust elastin-based hydrogel incorporating the lanthanide-binding protein, lanmodulin, for efficient and selective REE separation. A fusion protein of elastin-like polypeptide and lanmodulin was synthesized and cross-linked with four-arm polyethylene glycol to form a porous network that enhances REE binding and release in aqueous environments. The protein-cross-linked hydrogel exhibits high internal selectivity for lanthanide ions over multiple regeneration cycles. When implemented as an ion exchange chromatography adsorbent, it enables the selective fractionation of lanthanides from allanite ore, a complex natural source containing abundant REEs and non-REEs. The combination of excellent selectivity and operational stability positions this protein hydrogel as a sustainable platform for eco-friendly REE separation and purification.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (149KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (149KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5878-5886"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypeptide Sequence Effects on Virus Thermostability in Complex Coacervate Formulations","authors":"Pratik U. Joshi,&nbsp;Claire Decker,&nbsp;Arvind Sathyavageeswaran,&nbsp;Xianci Zeng,&nbsp;Hong Liu,&nbsp;Milad Kheirvari,&nbsp;Ebenezer Tumban,&nbsp;Lynn Manchester,&nbsp;Idris Tohidian,&nbsp;Eduardo Barbieri,&nbsp;Sarah L. Perry,&nbsp;Caryn L. Heldt","doi":"10.1021/acs.biomac.6c00747","DOIUrl":"10.1021/acs.biomac.6c00747","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Current vaccine formulations heavily rely on cold chains to avoid degradation during transportation and storage. Vaccines typically degrade when exposed to temperatures outside the 2–8 °C range, leading to waste and logistical challenges, particularly in rural areas. This study investigates the ability of poly­(lysine)- and poly­(glutamate)-based peptide coacervates to improve the thermal stability of porcine parvovirus (PPV), a model nonenveloped viral vaccine. We hypothesized that both the length and specific amino acid sequence of the peptides forming the coacervates would influence the stability of PPV. Long polypeptides (400–800 mers) provided significant protection, slowing PPV inactivation at 60 °C for up to 7 days by as much as 4 logs (10,000-fold), whereas shorter 48-mer homopolypeptides offered limited stability. Modifying peptide sequences revealed that glutamate-glycine block copolypeptides at larger block sizes improved thermostability, while incorporating alanine residues into lysine block copolypeptides improved stabilization beyond that achieved with long homopolypeptides. The addition of sucrose in the formulations further improved thermostability, while trehalose showed minimal benefit. Although coacervation did not have a significant impact on viral infectivity, &lt;em&gt;in vivo&lt;/em&gt; studies leveraging an alum adjuvant demonstrated that PPV released from a coacervate yielded lower antibody responses compared to native virus, indicating the presence of complicating interactions that potentially masked the immunogenic epitopes on the capsid surface or decreased the effectiveness of the adjuvant. Overall, this study showed that coacervate formulations can be adjusted to enhance virus thermal stability; however, further work is necessary to understand how such formulations can provide thermostability without altering the immune response necessary for a successful vaccine. Such design principles would enable the development of formulations that could decrease the vaccine cold-chain dependence and improve vaccine accessibility.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Current vaccine formulations heavily rely on cold chains to avoid degradation during transportation and storage. Vaccines typically degrade when exposed to temperatures outside the 2–8 °C range, leading to waste and logistical challenges, particularly in rural areas. This study investigates the ability of poly­(lysine)- and poly­(glutamate)-based peptide coacervates to improve the thermal stability of porcine parvovirus (PPV), a model nonenveloped viral vaccine. We hypothesized that both the length and specific amino acid sequence of the peptides forming the coacervates would influence the stability of PPV. Long polypeptides (400–800 mers) provided significant protection, slowing PPV inactivation at 60 °C for up to 7 days by as much as 4 logs (10,000-fold), whereas shorter 48-mer homopolypeptides offered limited stability. Modifying peptide sequences revealed that glutamate-glycine block c","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5997-6008"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioorthogonal Click Chemistry Enables Stable Cell Attachment to Silk Fibroin Scaffolds for Tissue Engineering Applications: Proof of Concept in Neural Regeneration","authors":"Ana Quintana-Prego,&nbsp;Atocha Guedan-Duran,&nbsp;Gustavo Victor Guinea,&nbsp;Juan Gomez-Rivas,&nbsp;Fivos Panetsos","doi":"10.1021/acs.biomac.6c01009","DOIUrl":"10.1021/acs.biomac.6c01009","url":null,"abstract":"<div><div>Tissue engineering seeks effective strategies to integrate cells into scaffolds while preserving spatial organization and stability. Conventional approaches based on extracellular matrix molecules or adhesion peptides often provide weak and nonspecific attachments, limiting robust assembly of complex cellular architectures. Here, we investigate biorthogonal click chemistry to address these limitations. By enabling covalent cell-biomaterial bonding through strain-promoted azide–alkyne cycloaddition (SPAAC), we achieved stable cell-scaffold integration. As a proof of concept, we engineered artificial Bands of Büngner-like scaffolds by functionalizing silk microfibers with cyclooctyne groups and metabolically engineering Schwann cells to present azide functionalities. Over 15 days <em>in vitro</em>, these biohybrid scaffolds supported directed neurite outgrowth, preserved metabolic activity, and increased nerve growth factor levels at early time points. Our results support click chemistry as a robust strategy for assembling stable cell-laden scaffolds while preserving biological function, potentially enabling the tailored design of complex cellular architectures and microenvironments for tissue engineering applications.</div></div><div>Tissue engineering seeks effective strategies to integrate cells into scaffolds while preserving spatial organization and stability. Conventional approaches based on extracellular matrix molecules or adhesion peptides often provide weak and nonspecific attachments, limiting robust assembly of complex cellular architectures. Here, we investigate biorthogonal click chemistry to address these limitations. By enabling covalent cell-biomaterial bonding through strain-promoted azide–alkyne cycloaddition (SPAAC), we achieved stable cell-scaffold integration. As a proof of concept, we engineered artificial Bands of Büngner-like scaffolds by functionalizing silk microfibers with cyclooctyne groups and metabolically engineering Schwann cells to present azide functionalities. Over 15 days <em>in vitro</em>, these biohybrid scaffolds supported directed neurite outgrowth, preserved metabolic activity, and increased nerve growth factor levels at early time points. Our results support click chemistry as a robust strategy for assembling stable cell-laden scaffolds while preserving biological function, potentially enabling the tailored design of complex cellular architectures and microenvironments for tissue engineering applications.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (93KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (93KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 6096-6110"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Distinct Structural Propensities of Poly-C, A, and U Single-Stranded RNA","authors":"Tong Wang,&nbsp;Weiwei He,&nbsp;Scout Fronhofer,&nbsp;Serdal Kirmizialtin,&nbsp;Lois Pollack","doi":"10.1021/acs.biomac.6c00716","DOIUrl":"10.1021/acs.biomac.6c00716","url":null,"abstract":"<div><div>Homopolymeric single-stranded RNAs (ssRNAs) are common biological motifs, yet their sequence-dependent solution structures remain incompletely defined. Particularly, rC30 and rA30 have not been characterized with atomic detail. Using optimized force fields, we integrate small-angle X-ray scattering (SAXS) with SAXS-driven molecular dynamics to generate and refine conformational ensembles for thirty-nucleotide-long strands of poly­(rA), poly­(rC), and poly­(rU) (rA30, rC30, and rU30) in identical buffers. Scattering profiles are computed from refined MD-generated ensembles and accurately reproduce the SAXS measurements. Properties of these refined ensembles are further validated by circular dichroism (CD) and UV melting. Clear sequence-dependent order emerges: rA30 is the most compact and helical, rU30 is largely coil-like, and rC30 falls in between. Together, these cross-validated ensembles define distinct conformational propensities of ssRNA homopolymers, specifically highlighting poly­(rC) as a unique, moderately structured, yet highly heterogeneous ssRNA. These findings may have implications for nucleotide-specific macromolecular recognition.</div></div><div>Homopolymeric single-stranded RNAs (ssRNAs) are common biological motifs, yet their sequence-dependent solution structures remain incompletely defined. Particularly, rC30 and rA30 have not been characterized with atomic detail. Using optimized force fields, we integrate small-angle X-ray scattering (SAXS) with SAXS-driven molecular dynamics to generate and refine conformational ensembles for thirty-nucleotide-long strands of poly­(rA), poly­(rC), and poly­(rU) (rA30, rC30, and rU30) in identical buffers. Scattering profiles are computed from refined MD-generated ensembles and accurately reproduce the SAXS measurements. Properties of these refined ensembles are further validated by circular dichroism (CD) and UV melting. Clear sequence-dependent order emerges: rA30 is the most compact and helical, rU30 is largely coil-like, and rC30 falls in between. Together, these cross-validated ensembles define distinct conformational propensities of ssRNA homopolymers, specifically highlighting poly­(rC) as a unique, moderately structured, yet highly heterogeneous ssRNA. These findings may have implications for nucleotide-specific macromolecular recognition.</div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (84KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (84KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"27 9","pages":"Pages 5976-5983"},"PeriodicalIF":5.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148958023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}