Article
Chemistry, Multidisciplinary
Sarah E. Sandler, Robert I. Horne, Sara Rocchetti, Robert Novak, Nai-Shu Hsu, Marta Castellana Cruz, Z. Faidon Brotzakis, Rebecca C. Gregory, Sean Chia, Goncalo J. L. Bernardes, Ulrich F. Keyser, Michele Vendruscolo
Summary: This study presents a single-molecule approach using solid-state nanopores and multiplexed DNA barcoding for the detection and quantification of protein oligomers. By studying alpha-synuclein oligomers and inhibitors of alpha-synuclein aggregation, the potential applicability of this method to the development of diagnostic and therapeutic methods for Parkinson's disease is demonstrated.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Analytical
Chyi Wei Chung, Amberley D. Stephens, Edward Ward, Yuqing Feng, Molly Jo Davis, Clemens F. Kaminski, Gabriele S. Kaminski Schierle
Summary: This study proposes a label-free assay using intrinsic amyloid fluorescence lifetime and model-free phasor plots to characterize the amyloid structure. The unique fluorescence lifetimes of different amyloids and their polymorphic populations can differentiate them, and the disaggregation of fibrils leads to increased fluorescence lifetimes. This assay provides a medium-throughput method for rapid classification of amyloids and their polymorphs, as well as testing small-molecule inhibitory compounds.
ANALYTICAL CHEMISTRY
(2022)
Review
Nanoscience & Nanotechnology
Kabin Lin, Chen Chen, Congsi Wang, Peiyuan Lian, Yan Wang, Song Xue, Jingjie Sha, Yunfei Chen
Summary: Nanopores, as valuable single-molecule sensing tools, have been widely applied in the detection of various biological molecules. With the development of semiconductor fabrication techniques and materials science, nanopore preparation and modification technologies have made significant progress, providing us with more options.
Article
Genetics & Heredity
Blagovesta Popova, Dan Wang, Christina Paetz, Dagmar Akkermann, Diana F. Lazaro, Dajana Galka, Miriam Kolog Gulko, Markus T. Bohnsack, Wiebke Moebius, Katherine E. Bohnsack, Tiago F. Outeiro, Gerhard H. Braus
Summary: Research revealed that the expression of alpha-synuclein affects transcription levels in yeast and human cells, with the nucleolar DEAD-box helicase Dbp4 identified as a key modulator of alpha-synuclein toxicity. Interaction between alpha-synuclein and Dbp4/DDX10 leads to sub-cellular exclusion from the nucleolus and accumulation of toxic oligomeric species, presenting a novel perspective on Parkinson's disease complexity.
Article
Chemistry, Multidisciplinary
Yaxian Liu, Xiaoyi Wang, Giulia Campolo, Xiangyu Teng, Liming Ying, Joshua B. Edel, Aleksandar P. Ivanov
Summary: This study develops a strategy that combines nanopore-based sensing with molecular carriers to detect α-Synuclein oligomers directly in clinical samples, providing a new approach for the diagnosis and mechanism study of Parkinson's disease.
Article
Cell Biology
Lea Elsholz, Yasmine Wasser, Patrick Ziegler, Pardes Habib, Aaron Voigt
Summary: Inhibiting CK1 kinase activity by overexpressing CK1 binding protein (CK1BP) can reduce S129 phosphorylation, oligomerization, and insoluble accumulation of alpha-Syn. The results suggest that CK1BP may have beneficial effects on neurodegenerative diseases and represents a promising target for therapeutic approaches against alpha-synucleinopathies.
Review
Neurosciences
Juan Estaun-Panzano, Marie-Laure Arotcarena, Erwan Bezard
Summary: Synucleinopathies are a group of diseases characterized by the misfolding and aggregation of alpha-synuclein, leading to the formation of Lewy bodies. Studying the aggregation of alpha-synuclein is crucial for understanding these diseases, and recent breakthroughs have provided new insights into their mechanisms.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Chemistry, Physical
Vince St Dollente Mesias, Hongni Zhu, Xiao Tang, Xin Dai, Wei Liu, Yusong Guo, Jinqing Huang
Summary: This study demonstrates the potential interactions between SARS-CoV-2 protein segments and neuronal proteins, suggesting a potential risk of post-infection neurodegeneration. The receptor-binding domain of the spike protein can inhibit the fibrillization of neuronal proteins, while a segment of the envelope protein can accelerate the formation of oligomers. These findings provide important molecular insights into the neurological effects of SARS-CoV-2 infection and its association with Parkinson's disease.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Rohith K. Nellikka, Bhavya R. Bhaskar, Kinjal Sanghrajka, Swapnali S. Patil, Debasis Das
Summary: Alpha-synuclein plays a crucial role in the pathogenesis of Parkinson's disease by directly regulating individual exocytotic release events, controlling vesicular secretion. It forms an inhibitory complex to decrease the open probability of fusion pores, influenced by various factors. This study reveals the key role of alpha-synuclein in modulating pore properties and highlights its regulatory action in membrane fusion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
A. Raquel Esteves, Diana F. Silva, Diogo Banha, Emanuel Candeias, Beatriz Guedes, Sandra M. Cardoso
Summary: Sporadic Parkinson's disease (sPD) is a complex multifactorial disorder with unknown etiology. Our study reveals that lipopolysaccharide (LPS)-induced activation of innate immunity requires functional mitochondria and mimics PD pathology in cells. We also demonstrate that a-synuclein overproduction is an innate immune response, and mitochondria play a crucial role in innate immunity activation in idiopathic PD.
Article
Biochemistry & Molecular Biology
Christian Scheibe, Christiaan Karreman, Stefan Schildknecht, Marcel Leist, Karin Hauser
Summary: Alpha-synuclein is a crucial protein in Parkinson's disease, with interactions with membranes leading to aggregation and potential harm to the lipid structure. Other synucleins, such as beta-synuclein and alpha S Delta exon3, play a role in reducing membrane damage caused by alpha-synuclein aggregation. The imbalance of these synucleins may be a significant factor in neurodegenerative diseases.
Article
Materials Science, Multidisciplinary
Rui Hu, Wenlong Lu, Guanghao Wei, Hexin Nan, Juan Li, Qing Zhao
Summary: This study demonstrates label-free detection and detailed translocation dynamics study of Herceptin using solid-state nanopores, improving detection sensitivity and temporal resolution for probing structural information of single-molecule Herceptin.
ADVANCED MATERIALS TECHNOLOGIES
(2022)
Article
Biochemistry & Molecular Biology
Antoni Kowalski, Cristine Betzer, Sigrid Thirup Larsen, Emil Gregersen, Estella A. Newcombe, Montana Caballero Bermejo, Viktor Wisniewski Bendtsen, Jorin Diemer, Christina Ernstsen, Shweta Jain, Alicia Espina Bou, Annette Eva Langkilde, Lene N. Nejsum, Edda Klipp, Robert Edwards, Birthe B. Kragelund, Poul Henning Jensen, Poul Nissen
Summary: This study shows that monomeric alpha-synuclein can activate plasma membrane Ca2+-ATPase (PMCA) to promote calcium clearance in neurons. The colocalization of alpha-synuclein and PMCA at neuronal synapses suggests a potential physiological function for alpha-synuclein in regulating calcium expulsion.
Article
Biochemistry & Molecular Biology
Ary Lautaro Di Bartolo, Marcelo Caparotta, Diego Masone
Summary: It is now widely accepted that intrinsic disorder is closely related to the cell cycle, particularly in hybrid proteins with both structured and unstructured domains. This study focuses on how a-synuclein interacts with the nascent fusion pore during its expansion process. The intrinsically disordered region of a-synuclein is found to play a crucial role as a thermodynamic regulator of the nucleation-expansion energy barrier. In addition, the absence of this disordered region alters the protein interactions with PIP2 and POPS lipids, increasing the energy cost for the fusion pore to transition from nucleation to expansion.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Arati Tripathi, Heba Alnakhala, Elizabeth Terry-Kantor, Andrew Newman, Lei Liu, Thibaut Imberdis, Saranna Fanning, Silke Nuber, Nagendran Ramalingam, Dennis Selkoe, Ulf Dettmer
Summary: Alpha-synuclein plays a key role in Parkinson's disease. Missense mutations in the conserved N-terminus of the protein affect its interaction with the cell membrane. Two clinical mutants, E46K and G51D, were studied and compared. Both mutants showed altered membrane interactions, with E46K increasing and G51D decreasing the interactions. Cellular stress and reduced growth were observed in neurons and neuroblastoma cells expressing the mutants. The study suggests that reducing fatty-acid unsaturation could be a potential therapeutic strategy for preventing neurotoxicity in both E46K and G51D mutants.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Engineering, Biomedical
Hongbao Fang, Lianting Hu, Qixin Chen, Shanshan Geng, Kangqiang Qiu, Chengjun Wang, Mingang Hao, Zhiqi Tian, Huimin Chen, Lei Liu, Jun-Lin Guan, Yuncong Chen, Lei Dong, Zijian Guo, Weijiang He, Jiajie Diao
Summary: In this study, a stable super-resolution imaging probe was developed for the quantitative detection of endoplasmic reticulum (ER) damage and stress. This probe can selectively target ER and track changes in ER hydrophobicity during reticulophagy, a specific autophagy process, by fluorescence intensity and morphology. Additionally, a topological analytical tool was developed to detect structural changes in ER and quantitatively identify reticulophagy. Overall, the new probe and analytical strategy show promise for the detection and analysis of subtle ER damage and stress.
Article
Chemistry, Multidisciplinary
Kangqiang Qiu, Weiwei Zou, Zhou Fang, Yuxin Wang, Sam Bell, Xiang Zhang, Zhiqi Tian, Xiuqiong Xu, Baohua Ji, Dechang Li, Taosheng Huang, Jiajie Diao
Summary: With the development of nanotechnology, there is growing concern about the potential hazards of nanomaterials on human health, wildlife, and the environment. This study focuses on the impact of two typical 2D nanomaterials, MoS2 and BN nanosheets, on mitochondria, showing that they can penetrate the mitochondrial membrane and cause damages.
News Item
Biochemistry & Molecular Biology
Kangqiang Qiu, Zhiqi Tian, Jiajie Diao
Summary: A new pH nanosensor is developed to quantify the acidity level of lysosomes in cells and tumors by detecting shifts in near-infrared emission bands.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Rui Chen, Lei Wang, Guodong Ding, Guanqun Han, Kangqiang Qiu, Yujie Sun, Jiajie Diao
Summary: Endolysosome dynamics is crucial for autophagosome biogenesis. A cationic quinolinium-based fluorescent probe (PyQPMe) with pH-sensitive fluorescence in endolysosomes is reported here, enabling high-resolution imaging and deepening understanding of autophagy. The probe's large Stokes shift and strong fluorescence intensity reduce background noise, providing a high signal-to-noise ratio for imaging. Application of PyQPMe revealed a constant conversion rate from early to late endosomes/lysosomes during autophagy at the submicron level.
Review
Pharmacology & Pharmacy
Chengying Zhang, Zhiqi Tian, Rui Chen, Fiona Rowan, Kangqiang Qiu, Yujie Sun, Jun-Lin Guan, Jiajie Diao
Summary: Optical microscopes have advanced modern biomedicine and super-resolution microscopy (SRM) has become popular in the life sciences, especially in living cell imaging. SRM has been used to study drug delivery and kinetics at the subcellular level, providing insights into drug mechanisms and efficacy assessment. This paper reviews recent advances in SRM and its applications in assessing subcellular drug dynamics.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Biophysics
Rui Chen, Kangqiang Qiu, Daniel C. Y. Leong, Bidyut Kumar Kundu, Chengying Zhang, Prasenjit Srivastava, Katie E. White, Guodong Li, Guanqun Han, Ziyuan Guo, Christopher G. Elles, Jiajie Diao, Yujie Sun
Summary: This article introduces three new small-molecule probes with good fluorescence quantum yield and aqueous solubility, which exhibit excellent two-photon absorption in the near-infrared region. Lyso-2arm and Mito-3arm show good targeting abilities for lysosomes and mitochondria, respectively. In two-photon microscopy experiments, Mito-3arm outperforms a commercial two-photon dye, delivering enhanced resolution, broader NIR light excitation window, and higher signal-to-noise ratio. Moreover, the two-photon bioimaging of 3D human forebrain organoids confirms the successful deep tissue imaging capabilities of both Lyso-2arm and Mito-3arm. Overall, this work presents a rational design strategy for developing competent two-photon-absorbing probes by varying the number of conjugated arms for bioimaging applications.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Chemistry, Physical
Owen Tyoe, Chinta Aryal, Jiajie Diao
Summary: In this study, we used molecular dynamics simulation to reveal that docosahexaenoic acid (DHA) enhances the binding affinity between α-Synuclein (α-Syn) and lipid membranes by increasing electrostatic interaction energy. This promotes synaptic-like vesicle clustering via α-Syn interaction. Our findings provide insights into how DHA regulates α-Syn-mediated vesicle clustering, shedding light on its physiological and pathological role.
EUROPEAN PHYSICAL JOURNAL E
(2023)
Article
Biochemistry & Molecular Biology
Bing Bu, Zhiqi Tian, Dechang Li, Kai Zhang, Wei Chen, Baohua Ji, Jiajie Diao
Summary: In this study, it was demonstrated that the V-shape double transmembrane domains (dTMDs) of syntaxin 17 significantly reduce fusion rate compared with the single transmembrane domain (sTMD). Theoretical analysis revealed that the V-shape dTMDs can increase protein-lipid mismatch, thereby raising the energy barrier of fusion. Increasing the number of SNAREs can reduce the energy barrier or protein-lipid mismatch. This study provides a physicochemical mechanistic understanding of SNARE-regulated membrane fusion.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Materials Science, Multidisciplinary
Xintian Shao, Zhou Fang, Miaoling Li, Weiwei Zou, Qianchun Wang, Chengying Zhang, Yongchun Wei, Zhiqi Tian, Yongchao Lai, Yunxia Cao, Baohua Ji, Dechang Li, Qixin Chen, Jiajie Diao
Summary: Graphene oxide (GO)-based nanomaterials have unique properties that make them highly interesting for biomedical research and nanomedicine. This study reveals that GO nanosheets can damage mitochondrial membranes and disrupt mitochondrial cristae, with the size of the nanosheets playing a crucial role. These findings highlight the importance of evaluating the effects of GO-based tools and products on mitochondria.
ACS MATERIALS LETTERS
(2023)
Article
Biotechnology & Applied Microbiology
Yuxin Wang, Yun-Sheng Chan, Matthew Chae, Donglu Shi, Chen-Yi Lee, Jiajie Diao
Summary: Biochips, a novel technology in biomolecular analysis, provide a compact and efficient solution for testing needs by integrating multiple functions in a single system. The pattern-control micro-electrode-dot-array (MEDA) design in biochips offers universality, replacing microchannels and enabling programmable control and dynamic grouping of electrodes for diverse testing requirements. This paper presents a visible biochip testing system that tracks the testing process in real time, and demonstrates its application in SARS-CoV-2 detection.
BIOENGINEERING-BASEL
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Yun-Sheng Chan, Jiajie Diao, Chen-Yi Lee
Summary: A pattern-control digital biochip is proposed for fast medical tests, which can achieve digital microfluidic operations, capacitive sensing, and thermal cycle via different control patterns. Preliminary measurements show that each thermal cycle for polymerase chain reaction (PCR) can be completed in less than 20 seconds with power consumption of 256-444 uW per micro-electrode while dealing with nano-liter samples.
2023 IEEE INTERNATIONAL SYMPOSIUM ON CIRCUITS AND SYSTEMS, ISCAS
(2023)
Article
Cell Biology
Qixin Chen, Liu-Yi Liu, Zhiqi Tian, Zhou Fang, Kang-Nan Wang, Xintian Shao, Chengying Zhang, Weiwei Zou, Fiona Rowan, Kangqiang Qiu, Baohua Ji, Jun-Lin Guan, Dechang Li, Zong-Wan Mao, Jiajie Diao
Summary: In this study, a dual-color fluorescent probe called mtGLP was developed to monitor the dynamics of mitochondrial membrane and mtDNA simultaneously. Through experiments and simulations, it was discovered that nucleoid condensates utilize peripheral fission to maintain mitochondrial homeostasis.
Article
Chemistry, Multidisciplinary
Rui Chen, Kangqiang Qiu, Guanqun Han, Bidyut Kumar Kundu, Guodong Ding, Yujie Sun, Jiajie Diao
Summary: Using the fluorescent probe PCV-1 under super-resolution microscopy, this study visualized cell viability and developed an analytical assay called organelle ratiometric probing (ORP) for quantitative analysis and assessment of individual cell viability. This method is of great significance in gaining deeper insights into the mechanisms of cell death.
Article
Chemistry, Multidisciplinary
Rui Chen, Kangqiang Qiu, Guanqun Han, Bidyut Kumar Kundu, Guodong Ding, Yujie Sun, Jiajie Diao
Summary: Detecting cell viability at the single-cell level is crucial in cancer research. We have developed a fluorescent probe, PCV-1, which can visualize cell viability under super-resolution imaging. By comparing the fluorescence intensity of mitochondria and nucleoli, we have developed an analytical assay named ORP to quantitatively analyze and assess cell viability at the single-cell level.
Review
Chemistry, Analytical
Xiuqiong Xu, Kangqiang Qiu, Zhiqi Tian, Chinta Aryal, Fiona Rowan, Rui Chen, Yujie Sun, Jiajie Diao
Summary: This review provides an overview of the application of structured illumination microscopy (SIM) in the study of subcellular structures, including its working principle, types of fluorescence probes, and quantitative analysis methods. The article also discusses the future directions for the development of this technology.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
