BiomacromoleculesPub Date : 2025-03-17DOI: 10.1021/acs.biomac.4c01749
Charaf Eddine Merzougui, Patrice Bacchin, Pierre Aimar, Christel Causserand, Pierre Roblin
{"title":"Analysis of HSA-PAA Complexation Using SEC-SAXS Combination: Unraveling Stoichiometry, Reversibility, and Interaction Specificity.","authors":"Charaf Eddine Merzougui, Patrice Bacchin, Pierre Aimar, Christel Causserand, Pierre Roblin","doi":"10.1021/acs.biomac.4c01749","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01749","url":null,"abstract":"<p><p>This work leverages the integration of size exclusion chromatography (SEC) with small-angle X-ray scattering (SAXS) to investigate the complex interactions between human serum albumin (HSA) and poly(acrylic acid) (PAA). The SEC-SAXS approach is proven in this study to effectively eliminate aggregates, enhancing data quality and revealing intricate details of protein-polymer associations. Initial findings demonstrate that HSA maintains its native structure across pH 5-8 and that HSA shows no significant interaction with the neutral polyethylene glycol (PEG). This highlights the critical role of charge regulation and electrostatic forces in HSA-PAA complex formation previously reported and the specificity of this interaction. The study further reveals that the HSA-PAA complex stoichiometry is highly dependent on PAA size, with larger PAA chains forming more elongated structures. The binding stoichiometry is then shown to increase nonlinearly, suggesting a delicate balance between attractive HSA-PAA and repulsive HSA-HSA interactions. Notably, HSA-PAA complexes exhibit reversible behavior, dissociating at pH > 5 and in media devoid of PAA.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646492","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}
BiomacromoleculesPub Date : 2025-03-14DOI: 10.1021/acs.biomac.5c0008610.1021/acs.biomac.5c00086
Qingjing Niu, Ke Shang, Huimin Han, Binlin Chen, Kongying Zhu, Lixia Ren and Xiaoyan Yuan*,
{"title":"Side-Functionalization of Poly(l-methionine) for Ice Control","authors":"Qingjing Niu, Ke Shang, Huimin Han, Binlin Chen, Kongying Zhu, Lixia Ren and Xiaoyan Yuan*, ","doi":"10.1021/acs.biomac.5c0008610.1021/acs.biomac.5c00086","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00086https://doi.org/10.1021/acs.biomac.5c00086","url":null,"abstract":"<p >Controlling ice growth is crucial during the cryopreservation of cells, but the current application of small molecules as cryoprotectants still remains a challenge. Inspired by structures of natural antifreeze (glyco)proteins, in this work, functionalized poly(<span>l</span>-methionine)s (PMets) are synthesized with different side groups including hydroxyl, threonine-mimetic with both methyl and hydroxyl groups (PMet-MOH), zwitterion with carboxyl and sulfonium (PMet-COOH), glycerol, and trehalose pendants. Results suggest that these functionalized PMets tend to self-assemble into 100–300 nm nanoparticles with positive charges in water. The functional structures have a remarkable influence on their ice control properties. It is supposed that PMet-MOH inhibits ice growth possibly through the adsorption mechanism by adjacent methyl and hydroxyl groups, whereas trehalose-tethered PMet can restrict diffusion of water molecules with the strongest ice recrystallization inhibition activity and zwitterionic PMet-COOH promotes ice nucleation obviously. This work offers valuable insight into the development of functional polypeptides as promising biocompatible cryoprotectants.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 4","pages":"2625–2636 2625–2636"},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825235","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}
BiomacromoleculesPub Date : 2025-03-14DOI: 10.1021/acs.biomac.5c0003610.1021/acs.biomac.5c00036
Aiman Sadaf, Hong Sik Yun, Hajin Lee, Samantha Stanfield, Baoliang Lan, Kristine Salomon, Menebere Woubshete, Seonghoon Kim, Muhammad Ehsan, Hyemi Bae, Bernadette Byrne, Claus J. Loland, Xiangyu Liu, Lan Guan, Wonpil Im and Pil Seok Chae*,
{"title":"Multiple Pendants-Bearing Triglucosides for Membrane Protein Studies: Effects of Pendant Length and Number on Micelle Interior Hydration and Protein Stability","authors":"Aiman Sadaf, Hong Sik Yun, Hajin Lee, Samantha Stanfield, Baoliang Lan, Kristine Salomon, Menebere Woubshete, Seonghoon Kim, Muhammad Ehsan, Hyemi Bae, Bernadette Byrne, Claus J. Loland, Xiangyu Liu, Lan Guan, Wonpil Im and Pil Seok Chae*, ","doi":"10.1021/acs.biomac.5c0003610.1021/acs.biomac.5c00036","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00036https://doi.org/10.1021/acs.biomac.5c00036","url":null,"abstract":"<p >Membrane proteins play central roles in cell physiology and are the targets of over 50% of FDA-approved drugs. In the present study, we prepared single alkyl-chained triglucosides decorated with multiple pendants, designated multiple pendant-bearing glucosides (MPGs), to enhance membrane protein stability. The new detergents feature two and four pendants of varying size at the hydrophilic–lipophilic interfaces, designated MPG-Ds and MPG-Ts, respectively. When tested with model membrane proteins, including the human adrenergic receptor (β<sub>2</sub>AR), the tetra-pendant-bearing MPGs (MPG-Ts) demonstrated superior performance compared to the dipendant analogs (MPG-Ds) and the gold standard DDM. All-atom molecular dynamics (MD) simulations results reveal that the four-pendant configuration of this detergent is remarkably effective in excluding water from the hydrophobic micelle interiors compared to the dipendant MPGs and DDM, an unprecedented feature of this new detergent. Our findings provide a novel strategy for designing water-resistant detergents, advancing the field of membrane protein research.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 4","pages":"2565–2579 2565–2579"},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825236","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":"Side-Functionalization of Poly(l-methionine) for Ice Control.","authors":"Qingjing Niu, Ke Shang, Huimin Han, Binlin Chen, Kongying Zhu, Lixia Ren, Xiaoyan Yuan","doi":"10.1021/acs.biomac.5c00086","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00086","url":null,"abstract":"<p><p>Controlling ice growth is crucial during the cryopreservation of cells, but the current application of small molecules as cryoprotectants still remains a challenge. Inspired by structures of natural antifreeze (glyco)proteins, in this work, functionalized poly(l-methionine)s (PMets) are synthesized with different side groups including hydroxyl, threonine-mimetic with both methyl and hydroxyl groups (PMet-MOH), zwitterion with carboxyl and sulfonium (PMet-COOH), glycerol, and trehalose pendants. Results suggest that these functionalized PMets tend to self-assemble into 100-300 nm nanoparticles with positive charges in water. The functional structures have a remarkable influence on their ice control properties. It is supposed that PMet-MOH inhibits ice growth possibly through the adsorption mechanism by adjacent methyl and hydroxyl groups, whereas trehalose-tethered PMet can restrict diffusion of water molecules with the strongest ice recrystallization inhibition activity and zwitterionic PMet-COOH promotes ice nucleation obviously. This work offers valuable insight into the development of functional polypeptides as promising biocompatible cryoprotectants.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622858","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}
BiomacromoleculesPub Date : 2025-03-14DOI: 10.1021/acs.biomac.5c00036
Aiman Sadaf, Hong Sik Yun, Hajin Lee, Samantha Stanfield, Baoliang Lan, Kristine Salomon, Menebere Woubshete, Seonghoon Kim, Muhammad Ehsan, Hyemi Bae, Bernadette Byrne, Claus J Loland, Xiangyu Liu, Lan Guan, Wonpil Im, Pil Seok Chae
{"title":"Multiple Pendants-Bearing Triglucosides for Membrane Protein Studies: Effects of Pendant Length and Number on Micelle Interior Hydration and Protein Stability.","authors":"Aiman Sadaf, Hong Sik Yun, Hajin Lee, Samantha Stanfield, Baoliang Lan, Kristine Salomon, Menebere Woubshete, Seonghoon Kim, Muhammad Ehsan, Hyemi Bae, Bernadette Byrne, Claus J Loland, Xiangyu Liu, Lan Guan, Wonpil Im, Pil Seok Chae","doi":"10.1021/acs.biomac.5c00036","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00036","url":null,"abstract":"<p><p>Membrane proteins play central roles in cell physiology and are the targets of over 50% of FDA-approved drugs. In the present study, we prepared single alkyl-chained triglucosides decorated with multiple pendants, designated multiple pendant-bearing glucosides (MPGs), to enhance membrane protein stability. The new detergents feature two and four pendants of varying size at the hydrophilic-lipophilic interfaces, designated MPG-Ds and MPG-Ts, respectively. When tested with model membrane proteins, including the human adrenergic receptor (β<sub>2</sub>AR), the tetra-pendant-bearing MPGs (MPG-Ts) demonstrated superior performance compared to the dipendant analogs (MPG-Ds) and the gold standard DDM. All-atom molecular dynamics (MD) simulations results reveal that the four-pendant configuration of this detergent is remarkably effective in excluding water from the hydrophobic micelle interiors compared to the dipendant MPGs and DDM, an unprecedented feature of this new detergent. Our findings provide a novel strategy for designing water-resistant detergents, advancing the field of membrane protein research.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629978","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":"Regulating the Characteristic Networks of Biodegradable Poly(l-malic acid-ε-caprolactone) Shape-Memory Materials: From Plastics to Elastomers.","authors":"Jing Song, Jiali Jiao, Chenguang Jiang, Yaxin Qiu, Defeng Wu","doi":"10.1021/acs.biomac.5c00163","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00163","url":null,"abstract":"<p><p>Developing new biodegradable polyesters with well-defined structures is of interest. We reported an attractive two-component aliphatic polyester-based thermoset, which was prepared via the esterification of biomass-derived l-malic acid oligomers and three-arm poly(ε-caprolactone) (3a-PCL) triols. The chemical network formed via the ester bonding and physical network caused by the crystallization of a 3a-PCL arm chain coexist in the thermoset, and the competition of the two characteristic networks leads to a negative correlation between the degree of covalent cross-linking and the degree of crystallization; thereby, the mechanical state of the thermosets can be easily tuned: from the plastic to elastomer state. Moreover, the crystallization temperature and melting point of the thermosets range in 30 °C ∼ 50 °C and -7 °C ∼ 18 °C, respectively, which are favorable for shape morphing as the thermosets are used as shape-memory materials. This work also provides valuable information about tailoring the mechanical and thermal properties of star-shaped polyester-based thermosets.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622854","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}
BiomacromoleculesPub Date : 2025-03-13DOI: 10.1021/acs.biomac.4c01759
Cristina Romo-Valera, Eric A Appel, Jaime Etxebarria, Jon Arluzea, Noelia Andollo
{"title":"In Vitro Evaluation of Gelatin-Based Hydrogels as Potential Fillers for Corneal Wounds.","authors":"Cristina Romo-Valera, Eric A Appel, Jaime Etxebarria, Jon Arluzea, Noelia Andollo","doi":"10.1021/acs.biomac.4c01759","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01759","url":null,"abstract":"<p><p>Corneal persistent epithelial defects are common ophthalmic injuries that can cause significant visual and structural damage. While diagnosis is straightforward, treatment remains challenging. Noninvasive therapies like eye drops are preferred, but severe neurotrophic keratopathy may require surgical interventions. This study explores gelatin-based hydrogels as noninvasive alternatives for corneal repair. Four photo-cross-linkable hydrogels with gelatin and riboflavin phosphate (RFP) were evaluated: a control and variants incorporating 2.5% dextran (D), 0.4% hyaluronic acid (HA), or 1% methylcellulose (MC). In vitro assessments included physicochemical properties, biocompatibility, and release kinetics alongside ex vivo wound healing assays. The gelatin-RFP hydrogel maintained corneal transparency, while additives reduced it. Dextran slowed compound release, and HA and MC reduced the release rate of larger molecules. All hydrogels showed excellent biocompatibility, and ex vivo models confirmed re-epithelialization, though slower than controls. The unmodified gelatin-RFP hydrogel demonstrated the best potential for corneal tissue engineering, supporting its future clinical translation.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622853","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":"Regulating the Characteristic Networks of Biodegradable Poly(l-malic acid-ε-caprolactone) Shape-Memory Materials: From Plastics to Elastomers","authors":"Jing Song, Jiali Jiao, Chenguang Jiang, Yaxin Qiu* and Defeng Wu*, ","doi":"10.1021/acs.biomac.5c0016310.1021/acs.biomac.5c00163","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00163https://doi.org/10.1021/acs.biomac.5c00163","url":null,"abstract":"<p >Developing new biodegradable polyesters with well-defined structures is of interest. We reported an attractive two-component aliphatic polyester-based thermoset, which was prepared via the esterification of biomass-derived <span>l</span>-malic acid oligomers and three-arm poly(ε-caprolactone) (3a-PCL) triols. The chemical network formed via the ester bonding and physical network caused by the crystallization of a 3a-PCL arm chain coexist in the thermoset, and the competition of the two characteristic networks leads to a negative correlation between the degree of covalent cross-linking and the degree of crystallization; thereby, the mechanical state of the thermosets can be easily tuned: from the plastic to elastomer state. Moreover, the crystallization temperature and melting point of the thermosets range in 30 °C ∼ 50 °C and −7 °C ∼ 18 °C, respectively, which are favorable for shape morphing as the thermosets are used as shape-memory materials. This work also provides valuable information about tailoring the mechanical and thermal properties of star-shaped polyester-based thermosets.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 4","pages":"2720–2732 2720–2732"},"PeriodicalIF":5.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825172","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":"Synthetic Strategy to Build High-Molecular-Weight Poly(L-tyrosine) and Its Unexplored β-Sheet Block Copolymer Nanoarchitectures.","authors":"Parshuram Kambale, Rahul Nisal, Manickam Jayakannan","doi":"10.1021/acs.biomac.5c00046","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00046","url":null,"abstract":"<p><p>Synthesis of high-molecular-weight polypeptides and their block copolymer macromolecular architectures from β-sheet-promoting L-amino acids is still an unresolved problem. Here, an elegant steric hindrance-assisted ring-opening polymerization (SHAROP) strategy is introduced to access β-sheet poly(L-tyrosine) having more than 250 units. The scope of the synthetic methodology is expanded to access unexplored poly(L-tyrosine)-based higher-order β-sheet block copolymer nanoassemblies. In this strategy, a <i>tert-</i>butyl benzyl unit is employed as a steric handle that imbibes the solubility by promoting the α-helical conformation in the propagating polypeptide chains. The living ROP process enables the synthesis of well-defined block copolymers initiated by poly(L-tyrosine) living-chain ends or growing the poly(L-tyrosine) chains from the pre-existing macroinitiators of poly(L-glutamate) or poly(L-lysine). Acid-catalyzed postpolymerization deprotection restores the poly(L-tyrosine) blocks in their nascent β-sheet conformations. Thioflavin-T fluorescence assay establishes the β-sheet core-shell structures of these nanoassemblies, which are found to be nontoxic to mammalian cell lines.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612819","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}
BiomacromoleculesPub Date : 2025-03-12DOI: 10.1021/acs.biomac.5c0004610.1021/acs.biomac.5c00046
Parshuram Kambale, Rahul Nisal and Manickam Jayakannan*,
{"title":"Synthetic Strategy to Build High-Molecular-Weight Poly(L-tyrosine) and Its Unexplored β-Sheet Block Copolymer Nanoarchitectures","authors":"Parshuram Kambale, Rahul Nisal and Manickam Jayakannan*, ","doi":"10.1021/acs.biomac.5c0004610.1021/acs.biomac.5c00046","DOIUrl":"https://doi.org/10.1021/acs.biomac.5c00046https://doi.org/10.1021/acs.biomac.5c00046","url":null,"abstract":"<p >Synthesis of high-molecular-weight polypeptides and their block copolymer macromolecular architectures from β-sheet-promoting <span>L</span>-amino acids is still an unresolved problem. Here, an elegant steric hindrance-assisted ring-opening polymerization (SHAROP) strategy is introduced to access β-sheet poly(<span>L</span>-tyrosine) having more than 250 units. The scope of the synthetic methodology is expanded to access unexplored poly(<span>L</span>-tyrosine)-based higher-order β-sheet block copolymer nanoassemblies. In this strategy, a <i>tert-</i>butyl benzyl unit is employed as a steric handle that imbibes the solubility by promoting the α-helical conformation in the propagating polypeptide chains. The living ROP process enables the synthesis of well-defined block copolymers initiated by poly(<span>L</span>-tyrosine) living-chain ends or growing the poly(<span>L</span>-tyrosine) chains from the pre-existing macroinitiators of poly(<span>L</span>-glutamate) or poly(<span>L</span>-lysine). Acid-catalyzed postpolymerization deprotection restores the poly(<span>L</span>-tyrosine) blocks in their nascent β-sheet conformations. Thioflavin-T fluorescence assay establishes the β-sheet core–shell structures of these nanoassemblies, which are found to be nontoxic to mammalian cell lines.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 4","pages":"2580–2600 2580–2600"},"PeriodicalIF":5.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825186","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}