{"title":"Viscoelastic Behavior of Aqueous Hydroxypropyl Cellulose Solutions Due to Entanglements.","authors":"Misato Yoshida, Hyota Hozumi, Yoshiki Horikawa, Toshiyuki Shikata","doi":"10.1021/acs.biomac.4c01646","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01646","url":null,"abstract":"<p><p>Hydroxypropyl cellulose (HpC) forms a liquid crystalline phase and is thought to have a rod-like shape in aqueous solution. The viscoelastic behaviors of aqueous solutions of HpC samples with average molar substitution numbers (<i>MS</i> ∼ 3.8) and weight-average molar masses (<i>M</i><sub>w</sub> = 36-740 kg mol<sup>-1</sup>) were examined over a wide concentration (<i>c</i>) range, and the results were discussed based on a concept of rod particle suspension rheology. The <i>c</i> and <i>M</i><sub>w</sub> dependencies of viscoelastic parameters determined in the frequency range showing flow behavior, such as the zero-shear viscosity, the average relaxation time, and the steady-state compliance in the <i>c</i> range for HpC molecules to fully entangle, were considered by using the number density (ν = <i>cN</i><sub>A</sub>/<i>M</i><sub>w</sub>, where <i>N</i><sub>A</sub> is the Avogadro constant), the intrinsic viscosity, and the average rod particle length of HpC molecules determined via dilute solution properties. The obtained relationships were successfully understood with the rod particle suspension rheology.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996239","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 : 2025-01-14DOI: 10.1021/acs.biomac.4c01321
Fei Guo, Jun Xiang, Yue Zhuo, Kai Pei
{"title":"Molecular Dynamics Study of Protein-Mediated Electroporation of Kv Channels Induced by nsPEFs: Advantages of Bipolar Pulses.","authors":"Fei Guo, Jun Xiang, Yue Zhuo, Kai Pei","doi":"10.1021/acs.biomac.4c01321","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01321","url":null,"abstract":"<p><p>Nanosecond pulsed electric fields (nsPEFs) can induce protein-mediated electroporation (PMEP) in voltage-gated ion channels. However, their effects on the tetrameric structure of voltage-gated potassium (Kv) channels remain unexplored. Our study pioneered the molecular dynamics (MD) investigation of the open-state (O) Kv channel to understand the effects of PMEP under unipolar and bipolar pulses (UP and BP). Our findings revealed that BP induces pore formation more effectively than UP. Additionally, the frequency of pore formation shows a more consistent decline with increased pulse interval under BP. We further examined three other distinct functional states─intermediate (C*), inactivated (I), and resting closed (C)─of Kv channels under BP. SF pores formed exclusively in the O state, while complex pores formed only in the O and C states. In conclusion, our study highlights BP's role in enhancing pore formation and specificity, offering insights into Kv channel PMEP and its therapeutic potential.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982317","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 : 2025-01-14DOI: 10.1021/acs.biomac.4c01516
Eugenia Apuzzo, Marilina Cathcarth, Agustín S Picco, Catalina von Bilderling, Omar Azzaroni, Maximiliano L Agazzi, Santiago E Herrera
{"title":"Insights into the Mechanism of Protein Loading by Chain-Length Asymmetric Complex Coacervates.","authors":"Eugenia Apuzzo, Marilina Cathcarth, Agustín S Picco, Catalina von Bilderling, Omar Azzaroni, Maximiliano L Agazzi, Santiago E Herrera","doi":"10.1021/acs.biomac.4c01516","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01516","url":null,"abstract":"<p><p>The study of the phase behavior of polyelectrolyte complex coacervates has attracted significant attention in recent years due to their potential use as membrane-less organelles, microreactors, and drug delivery platforms. In this work, we investigate the mechanism of protein loading in chain-length asymmetric complex coacervates composed of a polyelectrolyte and an oppositely charged multivalent ion. Unlike the symmetric case (polycation + polyanion), we show that protein loading is highly selective based on the protein's net charge: only proteins with charges opposite to the polyelectrolyte can be loaded. Through a series of systematic experiments, we identified that the protein loading process relies on the formation of a neutral three-component coacervate in which both the protein and the multivalent ion serve as complexing agents for the polyelectrolyte. Lastly, we demonstrated that this mechanism extends to the sequestration of other charged small molecules, offering valuable insights into designing functional multicomponent coacervates.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976832","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 : 2025-01-13Epub Date: 2024-12-06DOI: 10.1021/acs.biomac.4c01462
Aram Shin, Seong Ryeol Choi, Jun Ho Yim, Eu Jin Chung, Seung Won Nam, Brendan P Burns, Young Jae Jeon, Byeong-Su Kim
{"title":"Synergistic Effect of Polyglycerol and DMSO for Long-Term Cryopreservation of <i>Stichococcus</i> Species.","authors":"Aram Shin, Seong Ryeol Choi, Jun Ho Yim, Eu Jin Chung, Seung Won Nam, Brendan P Burns, Young Jae Jeon, Byeong-Su Kim","doi":"10.1021/acs.biomac.4c01462","DOIUrl":"10.1021/acs.biomac.4c01462","url":null,"abstract":"<p><p>Herein, we present a significant advancement in long-term cryopreservation techniques for microalgae <i>Stichococcus</i> species using a combination of linear polyglycerol (<i>lin</i>PG) and dimethyl sulfoxide (DMSO). The technique was tested on three <i>Stichococcus</i> species: <i>Stichococcus bacillaris</i>, <i>Stichococcus deasonii</i>, and <i>Stichococcus minor</i>, which showed long-term viability and recovery rates superior to those when treated with a traditional cryoprotectant only. While DMSO alone enabled high cell recovery rates for all species after 1 week of cryopreservation, the rates for some of them dropped below 50% after 26 weeks of cryopreservation. Treating the cells with a combination of <i>lin</i>PG and DMSO raised the recovery rates for all three <i>Stichococcus</i> species to above 92% after long-term cryopreservation. Our findings indicate that <i>lin</i>PG in combination with DMSO offers a synergistic and effective solution for maintaining cell integrity and functionality during long-term cryopreservation of microalgae.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"635-643"},"PeriodicalIF":5.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790505","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 : 2025-01-13Epub Date: 2024-12-12DOI: 10.1021/acs.biomac.4c01257
Huanli Sun, Zhiyuan Zhong
{"title":"Bioresponsive Polymeric Nanoparticles: From Design, Targeted Therapy to Cancer Immunotherapy.","authors":"Huanli Sun, Zhiyuan Zhong","doi":"10.1021/acs.biomac.4c01257","DOIUrl":"10.1021/acs.biomac.4c01257","url":null,"abstract":"<p><p>Bioresponsive polymeric nanoparticles (NPs) that are capable of delivering and releasing therapeutics and biotherapeutics to target sites have attracted vivid interest in cancer therapy and immunotherapy. In contrast to enthusiastic evolution in the academic world, the clinical translation of these smart systems is scarce, partly due to concerns about safety, stability, complexity, and scalability. The moderate targetability, responsivity, and benefits are other concerns. In the past 17 years, we have devoted ourselves to exploring elegant strategies to address the above basic and translational problems by introducing diverse functional groups and/or targeting ligands to safe biomedical materials, such as biodegradable polymers and water-soluble polymers. This minimal modification is critical for further clinical translation. We have tailor-made various bioresponsive NPs including shell-sheddable and/or acid-sensitive biodegradable NPs, disulfide-cross-linked biodegradable micelles and polymersomes, and blood-brain barrier (BBB)-permeable NPs, to target different tumors. This perspective provides an overview of our work path toward targeted nanomedicines and personalized vaccines, which might inspire clinical translation and future research on cancer therapy.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"33-42"},"PeriodicalIF":5.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816658","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 : 2025-01-13Epub Date: 2024-12-09DOI: 10.1021/acs.biomac.4c01250
Manseok Yang, Sujin Kim, Seungwon Jeong, Suyeon Lee, Seunga Lee, Hanui Jo, Nuri Kim, Nanhee Song, Seong-Cheol Park, Dongwon Lee
{"title":"Harnessing Dual-Responsive Polymeric Micelles for Precision Oxidative Stress Amplification in Targeted Cancer Therapy.","authors":"Manseok Yang, Sujin Kim, Seungwon Jeong, Suyeon Lee, Seunga Lee, Hanui Jo, Nuri Kim, Nanhee Song, Seong-Cheol Park, Dongwon Lee","doi":"10.1021/acs.biomac.4c01250","DOIUrl":"10.1021/acs.biomac.4c01250","url":null,"abstract":"<p><p>Targeting the altered redox balance in cancer cells, this study explores a strategy to induce selective cancer cell death by combining reactive oxygen species (ROS) generation with glutathione (GSH) depletion. We developed oxidative stress-amplifying polymeric (pCB) micelles that function both as therapeutic agents and carriers for GSH-depleting retinoic acid prodrug (BRDP). pCB incorporating ROS-generating cinnamaldehyde and a GSH-depleting quinone methide precursor could self-assemble into micelles encapsulating BRDP, delivering both ROS generators and GSH-depleting drugs. The micelles were surface-functionalized with the tripeptide Arg-Gly-Asp (RGD) for targeted delivery to integrin-overexpressing tumors. In a mouse xenograft model, RGD-decorated BRDP-loaded micelles significantly accumulated in tumor sites, enhancing anticancer efficacy without toxicity to normal tissues. This study marks significant advancement in the field of oxidative stress-amplifying polymeric precursors, presenting a novel and highly effective anticancer therapeutic approach that integrates multiple tumor-specific triggers and ROS-mediated mechanisms.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"437-448"},"PeriodicalIF":5.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794031","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 : 2025-01-13Epub Date: 2024-12-13DOI: 10.1021/acs.biomac.4c00965
Yuheng Liu, Chuan Guo, Yu Wang, Qing-Quan Kong
{"title":"Application of an Injectable Thermosensitive Hydrogel Drug Delivery System for Degenerated Intervertebral Disc Regeneration.","authors":"Yuheng Liu, Chuan Guo, Yu Wang, Qing-Quan Kong","doi":"10.1021/acs.biomac.4c00965","DOIUrl":"10.1021/acs.biomac.4c00965","url":null,"abstract":"<p><p>Intervertebral disc degeneration is characterized by a localized, chronic inflammatory response leading to a synthesis/catabolism imbalance within the nucleus pulposus (NP) and progressive functional impairment within the NP. Polyphenol molecules have been widely used in anti-inflammatory therapies in recent years; therefore, we designed an injectable, temperature-sensitive hydrogel PLGA-PEG-PLGA-based drug delivery system for local and sustained delivery of two drugs tannic acid (TA) and resveratrol (Res), with the hydrogel carrying TA directly and Res indirectly (carried directly by inflammation-responsive nanoparticles). The delivery system presents good injectability at room temperature and forms a gel in situ upon entering the intervertebral disc. The delivery system can rapidly release TA and sustain Res release. In vitro and in vivo experiments have shown that this hydrogel drug delivery system is effective in anti-inflammation of degenerated intervertebral discs and promotes the regeneration of extracellular matrix in the NP.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"209-221"},"PeriodicalIF":5.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816654","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 : 2025-01-13Epub Date: 2024-12-17DOI: 10.1021/acs.biomac.4c00648
Md Nasir Uddin, Md Abu Monsur Dinar, Leah E Schrass, Daniel W Pack, Jason E DeRouchey
{"title":"Impact of Acetylation, Succinylation, and pH on DNA Packaging in PEI-Based Polyplexes.","authors":"Md Nasir Uddin, Md Abu Monsur Dinar, Leah E Schrass, Daniel W Pack, Jason E DeRouchey","doi":"10.1021/acs.biomac.4c00648","DOIUrl":"10.1021/acs.biomac.4c00648","url":null,"abstract":"<p><p>Polyethylenimine (PEI) is a widely used cationic polymer for nonviral gene delivery, often modified to enhance transfection efficiency and reduce cytotoxicity. This study investigates how acetylation, succinylation (acPEI and zPEI), and pH influence the internal DNA packaging of polyplexes. Both modifications alter physicochemical properties, leading to complexes that decondense more readily with increasing modification. X-ray scattering reveals that high acetylation produces loosely packed DNA, while succinylation unexpectedly tightens DNA packing at higher modification levels. Polyplexes formed at low pH (pH 4) are more stable and tightly packed than those formed at pH 7.5. Acidifying polyplexes initially formed at pH 7.5 induces structural rearrangement to tighter DNA packing accompanied by significant PEI release, providing direct evidence for models where free PEI aids endosomal escape. These findings challenge conventional assumptions about PEI behavior and offer new insights into DNA packaging, emphasizing tailored polymer modifications and pH conditions to optimize gene delivery.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"178-189"},"PeriodicalIF":5.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845301","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":"Flexible and Robust Piezoelectric Chitosan Films with Enhanced Bioactivity.","authors":"Srishti Chakraborty, Souvik Debnath, Kailas Mahipal Malappuram, Sampath Parasuram, Huan-Tsung Chang, Kaushik Chatterjee, Amit Nain","doi":"10.1021/acs.biomac.4c01464","DOIUrl":"https://doi.org/10.1021/acs.biomac.4c01464","url":null,"abstract":"<p><p>Chitosan (CHT) is a known piezoelectric biomacromolecule; however, its usage is limited due to rapid degradation in an aqueous system. Herein, we prepared CHT film via a solvent casting method and cross-linked in an alkaline solution. Sodium hydroxide facilitated deprotonation, leading to increased intramolecular hydrogen bonding and mechanical properties. The CHT film remained intact for 30 days in aqueous environments. A systematic study revealed a gradual increase in the output voltage from 0.9 to 1.8 V under external force (1-16 N). In addition, the CHT film showed remarkable antibacterial and anti-inflammatory activities under ultrasound stimulation and inhibition of inflammatory cytokines. The CHT films also displayed enhanced cellular proliferation and ∼5-fold faster migration of NIH3T3 cells under US stimulation. Overall, this work presents a robust, biocompatible, and wearable CHT device that can transform biomechanical energy into electrical pulses for the modulation of cell fate processes and other bioactivities.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968657","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 : 2025-01-13Epub Date: 2025-01-02DOI: 10.1021/acs.biomac.4c01261
Ying-Jen Shiu, Bradley W Mansel, Kuei-Fen Liao, Ting-Wei Hsu, Je-Wei Chang, Orion Shih, Yi-Qi Yeh, Johannes Allwang, U-Ser Jeng
{"title":"Revealing the Solution Conformation and Hydration Structure of Type I Tropocollagen Using X-ray Scattering and Molecular Dynamics Simulation.","authors":"Ying-Jen Shiu, Bradley W Mansel, Kuei-Fen Liao, Ting-Wei Hsu, Je-Wei Chang, Orion Shih, Yi-Qi Yeh, Johannes Allwang, U-Ser Jeng","doi":"10.1021/acs.biomac.4c01261","DOIUrl":"10.1021/acs.biomac.4c01261","url":null,"abstract":"<p><p>Hydration plays a crucial role in regulating the dispersion behavior of biomolecules in water, particularly in how pH-sensitive hydration water network forms around proteins. This study explores the conformation and hydration structure of Type-I tropocollagen using small- and wide-angle X-ray scattering (SWAXS) and molecular dynamics (MD) simulations. The results reveal that tropocollagen exhibits a significant softening conformation in solution, transitioning from its rod-like structure in tissues to a worm-like conformation, characterized by a reduced radius of gyration of 50 nm and a persistent length of 34 nm. The SWAXS-supported MD calculations further establish a hydration water network characterized by a 2.8 Å free-water exclusion zone where water molecules are largely hydrogen-bonded to the densely distributed polar groups on the tropocollagen surfaces. These first-layer water molecules are bridged by outer water molecules extending up to 4 Å from the protein surfaces, forming a major hydration shell that encapsulates the protein.</p>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":" ","pages":"449-458"},"PeriodicalIF":5.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}