Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema

Zihui Zheng,1,2,* Aobo Nie,1,* Xiaojie Wu,1 Shi Chen,1 Lijun Zhang,1 Dongqing Yang,3 Yuqing Shi,1 Xiyu Xiong,1 Jun Guo1,2 1Department of Biochemistry and Molecular Biology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of Chin...

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Main Authors: Zheng Z, Nie A, Wu X, Chen S, Zhang L, Yang D, Shi Y, Xiong X, Guo J
Format: Article
Language:English
Published: Dove Medical Press 2025-04-01
Series:International Journal of Nanomedicine
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Online Access:https://www.dovepress.com/electromechanical-regulation-underlying-protein-nanoparticle-induced-o-peer-reviewed-fulltext-article-IJN
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author Zheng Z
Nie A
Wu X
Chen S
Zhang L
Yang D
Shi Y
Xiong X
Guo J
author_facet Zheng Z
Nie A
Wu X
Chen S
Zhang L
Yang D
Shi Y
Xiong X
Guo J
author_sort Zheng Z
collection DOAJ
description Zihui Zheng,1,2,* Aobo Nie,1,* Xiaojie Wu,1 Shi Chen,1 Lijun Zhang,1 Dongqing Yang,3 Yuqing Shi,1 Xiyu Xiong,1 Jun Guo1,2 1Department of Biochemistry and Molecular Biology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 2State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 3Department of Public Health, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Guo, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China, Tel +86 13813909055, Email guoj@njucm.edu.cnPurpose: Osmotic imbalance is a critical driving force of cerebral edema. Protein nanoparticles (PNs) amplify intracellular osmotic effects by regulating membrane potential and homeostasis of water and multiple ions. This study has investigated how PNs control the neuronal swelling through electromechanical activity.Methods: The fluorescence resonance energy transfer (FRET)-based Vimentin force probe was used to real-time monitor the osmotic tension in neurons. Patch clamp and the living cell 3D imaging system were applied to explore the relationship between cell electromechanical activity and cell volume in different cytotoxic cell models. Cytoplasmic PN amount measured by the NanoSight instrument, ion contents detected by the freezing point osmometer and ion imaging were performed to investigate the role of PNs in regulating cell swelling.Results: We observed a close association between neuronal swelling and changes in osmotic tension and membrane potential. The tension effect of biological osmotic pressure (OP) relies on electromechanical cooperation induced by intracellular PN and Ca2+ levels. PNs increment results from cytoplasmic translocation of intracellular various proteins. Alterations in Ca2+ content are involved in the membrane potential transition between depolarization and hyperpolarization in a PN-dependent manner. Chemical signals-mediated sensitization of ion channels has an indispensable effect on PN-induced ion increments. Notably, aquaporin-mediated water influx recovers membrane potential and enhances osmotic tension controlling neuronal swelling.Conclusion: Our findings indicate that PNs, Ca2+, and water are pivotal in electromechanical cooperation and provide insights into the biological OP mechanisms underlying neurotoxic edema. Keywords: protein nanoparticle, electromechanical cooperation, osmotic tension, membrane potential, neuronal swelling
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spelling doaj-art-e432894b6f8e4a4eaa5fa1464e5970252025-08-20T03:17:53ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-04-01Volume 2041454163101802Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic EdemaZheng ZNie AWu XChen SZhang LYang DShi YXiong XGuo JZihui Zheng,1,2,* Aobo Nie,1,* Xiaojie Wu,1 Shi Chen,1 Lijun Zhang,1 Dongqing Yang,3 Yuqing Shi,1 Xiyu Xiong,1 Jun Guo1,2 1Department of Biochemistry and Molecular Biology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 2State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 3Department of Public Health, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Guo, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China, Tel +86 13813909055, Email guoj@njucm.edu.cnPurpose: Osmotic imbalance is a critical driving force of cerebral edema. Protein nanoparticles (PNs) amplify intracellular osmotic effects by regulating membrane potential and homeostasis of water and multiple ions. This study has investigated how PNs control the neuronal swelling through electromechanical activity.Methods: The fluorescence resonance energy transfer (FRET)-based Vimentin force probe was used to real-time monitor the osmotic tension in neurons. Patch clamp and the living cell 3D imaging system were applied to explore the relationship between cell electromechanical activity and cell volume in different cytotoxic cell models. Cytoplasmic PN amount measured by the NanoSight instrument, ion contents detected by the freezing point osmometer and ion imaging were performed to investigate the role of PNs in regulating cell swelling.Results: We observed a close association between neuronal swelling and changes in osmotic tension and membrane potential. The tension effect of biological osmotic pressure (OP) relies on electromechanical cooperation induced by intracellular PN and Ca2+ levels. PNs increment results from cytoplasmic translocation of intracellular various proteins. Alterations in Ca2+ content are involved in the membrane potential transition between depolarization and hyperpolarization in a PN-dependent manner. Chemical signals-mediated sensitization of ion channels has an indispensable effect on PN-induced ion increments. Notably, aquaporin-mediated water influx recovers membrane potential and enhances osmotic tension controlling neuronal swelling.Conclusion: Our findings indicate that PNs, Ca2+, and water are pivotal in electromechanical cooperation and provide insights into the biological OP mechanisms underlying neurotoxic edema. Keywords: protein nanoparticle, electromechanical cooperation, osmotic tension, membrane potential, neuronal swellinghttps://www.dovepress.com/electromechanical-regulation-underlying-protein-nanoparticle-induced-o-peer-reviewed-fulltext-article-IJNprotein nanoparticleelectromechanical cooperationosmotic tensionmembrane potentialneuronal swelling
spellingShingle Zheng Z
Nie A
Wu X
Chen S
Zhang L
Yang D
Shi Y
Xiong X
Guo J
Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema
International Journal of Nanomedicine
protein nanoparticle
electromechanical cooperation
osmotic tension
membrane potential
neuronal swelling
title Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema
title_full Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema
title_fullStr Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema
title_full_unstemmed Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema
title_short Electromechanical Regulation Underlying Protein Nanoparticle-Induced Osmotic Pressure in Neurotoxic Edema
title_sort electromechanical regulation underlying protein nanoparticle induced osmotic pressure in neurotoxic edema
topic protein nanoparticle
electromechanical cooperation
osmotic tension
membrane potential
neuronal swelling
url https://www.dovepress.com/electromechanical-regulation-underlying-protein-nanoparticle-induced-o-peer-reviewed-fulltext-article-IJN
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