Review
Cell Biology
Yaping Zhang, Samuel M. Ehrlich, Cheng Zhu, Xiaoping Du
Summary: The GPIb-IX complex plays a crucial role in mediating initial platelet adhesion and converting mechanical force into intracellular signals. Thrombin binding to GPIb-IX cooperatively stimulates platelet response. GPIb-IX signaling involves multiple pathways and molecular interactions, leading to calcium mobilization, integrin activation, and granule secretion.
Article
Hematology
M. Edward Quach, Wenchun Chen, Yingchun Wang, Hans Deckmyn, Francois Lanza, Bernhard Nieswandt, Renhao Li
Summary: The study identified a novel rat monoclonal antibody 3G6 that acts as a positive modulator of GPIb beta, enhancing GPIb-IX binding and activation. In contrast, another antibody RAM.1 inhibits GPIb-IX signaling, suggesting that changes in GPIb beta conformation may be crucial for outside-in activation via GPIb-IX.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Chemistry, Multidisciplinary
Michael S. Harris, Rachel F. Dolan, James R. Bryce, Jonas G. Ewusi, Gabriel A. Cook
Summary: Membrane glycoproteins are difficult to study but are linked to human diseases. Using membrane mimetics, researchers have successfully solubilized and performed glycosylation of a full-length membrane glycoprotein in nanodiscs, providing a biologically relevant sample to study the effects of the modification.
Article
Chemistry, Multidisciplinary
Bartholomaus Danielczak, Marie Rasche, Julia Lenz, Eugenio Perez Patallo, Sophie Weyrauch, Florian Mahler, Michael Tope Agbadaola, Annette Meister, Jonathan Oyebamiji Babalola, Carolyn Vargas, Cenek Kolar, Sandro Keller
Summary: Glyco-DIBMA, a novel glycopolymer, demonstrates enhanced efficiency in solubilizing lipid vesicles to form nanodiscs under near-physiological conditions, maintaining a bilayer structure and enabling rapid lipid exchange. Experimental results have shown the superior performance of Glyco-DIBMA in extracting cellular membrane proteins and analytical applications.
Article
Chemistry, Physical
Tetiana Mukhina, Yuri Gerelli, Arnaud Hemmerle, Alexandros Koutsioubas, Kirill Kovalev, Jean-Marie Teulon, Jean-Luc Pellequer, Jean Daillant, Thierry Charitat, Giovanna Fragneto
Summary: The proton pump transmembrane protein bacteriorhodopsin was successfully incorporated into planar floating lipid bilayers in gel and fluid phases using a detergent-mediated method. Neutron and X-ray reflectometry were employed to determine the structure and composition of the membrane protein system with sub-nanometer resolution, showing that lipid bilayer integrity and protein activity were preserved during the reconstitution process. Reversible structural modifications of the membrane induced by bacteriorhodopsin functional activity triggered by visible light were observed and characterized at the nanoscale.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Juanjuan Lu, Chunli Zhang, Shaohua Shi, Shaobai Li, Junling Liu, Jian Wu, Chenhui Huang, Ming Lei
Summary: GPIb-IX-V is an important platelet receptor involved in hemostasis and thrombosis. The structure and function of this complex are crucial for understanding bleeding and thrombosis.
BIOLOGICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Shukun Sun, Bao Qiao, Yu Han, Bailu Wang, Shujian Wei, Yuguo Chen
Summary: Platelets play a crucial role in normal hemostasis, but pathological platelet adhesion can lead to cardiovascular events. Traditional antithrombotic drugs have limited effects on platelet adhesion receptors, while posttranslational modifications (PTMs) can increase the functional diversity of these receptors and affect platelet processes. Targeting PTMs of platelet adhesion receptors with antithrombotic drugs may offer a new therapeutic approach.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Chemistry, Analytical
Hisatoshi Mimura, Toshihisa Osaki, Sho Takamori, Kenji Nakao, Shoji Takeuchi
Summary: This study proposes a device for repeated measurements of ion channels incorporated into individually arrayed lipid bilayers, overcoming the limitations of existing parallelized approaches. By optimizing the surface properties and clearance of a wiping blade module, the device achieves repeated bilayer formation and a 5-fold improvement in data throughput during ion channel activity measurements. The practical utility of the device is validated by evaluating the effects of an ion channel inhibitor. This device opens new avenues for high-throughput analysis and screening of ion channels, leading to significant advancements in drug discovery and functional studies of membrane proteins.
ANALYTICAL CHEMISTRY
(2023)
Article
Biophysics
Molly Y. Mollica, Kevin M. Beussman, Adithan Kandasamy, Lesley Martinez Rodriguez, Francisco R. Morales, Junmei Chen, Krithika Manohar, Juan C. del Alamo, Jose A. Lopez, Wendy E. Thomas, Nathan J. Sniadecki
Summary: Platelets form a hemostatic plug by binding to the subendothelium and to each other, and this binding is mediated by specific proteins. The morphology of platelet F-actin is related to traction forces and localization, and different F-actin patterns can affect the forces and positions of platelets.
BIOPHYSICAL JOURNAL
(2023)
Article
Hematology
Jing Wang, Yongxiang Gao, Lan Chen, Yugang Guo, Siyi Hu, Liansheng Cheng, Weihua Xiao, Jiyuan Ke, Zhongliang Zhu, Liwen Niu
Summary: Agkisacucetin, a novel antithrombotic drug candidate isolated from the venom of Deinagkistrodon acutus, specifically recognizes the platelet surface receptor to block thrombosis. The crystal structure reveals that Agkisacucetin primarily contacts GPIb alpha at specific regions to inhibit platelet function.
Article
Medicine, Research & Experimental
Wei Chu, Xuemei Sun, Xiaoxiao Zhu, Yu Chen Zhao, Jingcheng Zhang, Qin Kong, Lanlan Zhou
Summary: The study showed that the glycoprotein (GP) Ib antagonist anfibatide (ANF) mitigated blood-brain barrier (BBB) disruption after cerebral ischemia/reperfusion (CI/R) injury through activation of the Epac signaling pathway. ANF treatment improved tight junction protein expression, suppressed actin rearrangement, reduced brain tissue permeability, and alleviated brain edema. Additionally, ANF upregulated Epac1 protein expression in the ischemic cerebral cortex, demonstrating its protective effects on BBB integrity.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Juliane Baumann, Laura Sachs, Otto Oliver, Ingmar Schoen, Peter Nestler, Carlo Zaninetti, Martin Kenny, Ruth Kranz, Hendrik von Eysmondt, Johanna Rodriguez, Tilman E. Schaeffer, Zoltan Nagy, Andreas Greinacher, Raghavendra Palankar, Markus Bender
Summary: Patients with MYH9-related disease have a tendency for increased bleeding due to reduced platelet forces caused by mutations. Activation of mutant platelets is comparable to controls, but phosphorylation of myosin light chain is reduced. Treatment with tranexamic acid can improve hemostatic function.
Article
Dermatology
Silke M. Currie, Rebekka Stegmeyer, Karina Mildner, Leonhard Breitsprecher, Dagmar Zeuschner, Olympia Ekaterini Psathaki, Kerstin Schafer, Markus Wilkens, Stefan Volkery, Bernhard Nieswandt, Dietmar Vestweber
Summary: Platelets prevent neutrophil-induced hemorrhage in immune complex-mediated skin inflammation, preserving vascular integrity. By studying the single-cell dynamics of this process in real-time, researchers gained further insights into platelet recruitment and bleeding events.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Hematology
Marie A. Hollenhorst, Katherine H. Tiemeyer, Keira E. Mahoney, Kazuhiro Aoki, Mayumi Ishihara, Sarah C. Lowery, Valentina Rangel-Angarita, Carolyn R. Bertozzi, Stacy A. Malaker
Summary: This study comprehensively analyzed the glycosylation of platelet GPIbα and identified a diverse repertoire of N- and O-glycans. The findings lay the foundation for further research on the functional and structural roles of GPIbα glycans.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Pediatrics
Andrei K. Garzon Dasgupta, Alexey A. Martyanov, Anastasia A. Ignatova, Victor G. Zgoda, Galina A. Novichkova, Mikhail A. Panteleev, Anastasia N. Sveshnikova
Summary: This study showed that pediatric platelets have higher levels of proteins related to mitochondrial activity, proteasome activity, and vesicle transport. Additionally, pediatric platelets exhibited increased cytosolic calcium levels at rest, decreased calcium mobilization in response to ADP, and reduced granule release. These differences in protein composition and functional responses suggest that platelet behavior is age-dependent.
PEDIATRIC RESEARCH
(2023)
Article
Hematology
Yingchun Wang, Wenchun Chen, Wei Zhang, Melissa M. Lee-Sundlov, Caterina Casari, Michael C. Berndt, Francois Lanza, Wolfgang Bergmeier, Karin M. Hottmeister, X. Frank Zhang, Renhao Li
Summary: During infection, neuraminidase removes sialic acid from platelet GPIb alpha, leading to their rapid clearance. This mechanism may explain many puzzling and seemingly contradictory observations associated with clearance of desialylated or hyposialylated platelets.
Article
Chemistry, Multidisciplinary
Yuesong Hu, Victor Pui-Yan Ma, Rong Ma, Wenchun Chen, Yuxin Duan, Roxanne Glazier, Brian G. Petrich, Renhao Li, Khalid Salaita
Summary: This study developed a DNA-based microparticle tension sensor for investigating mechanotransduction at curved interfaces with high throughput. The method successfully mapped and measured T-cell receptor forces and platelet integrin forces, demonstrating its potential in screening drugs that modulate cellular mechanics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Hematology
M. Edward Quach, Wenchun Chen, Yingchun Wang, Hans Deckmyn, Francois Lanza, Bernhard Nieswandt, Renhao Li
Summary: The study identified a novel rat monoclonal antibody 3G6 that acts as a positive modulator of GPIb beta, enhancing GPIb-IX binding and activation. In contrast, another antibody RAM.1 inhibits GPIb-IX signaling, suggesting that changes in GPIb beta conformation may be crucial for outside-in activation via GPIb-IX.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Multidisciplinary Sciences
Nicholas A. Arce, Wenpeng Cao, Alexander K. Brown, Emily R. Legan, Moriah S. Wilson, Emma-Ruoqi Xu, Michael C. Berndt, Jonas Emsley, X. Frank Zhang, Renhao Li
Summary: The study reveals that the mechanism for activating Von Willebrand factor (VWF) in response to mechanical force is located in the autoinhibitory module, which can be unfolded by tensile force to activate VWF. Certain mutations or external factors can also affect the unfolding force of the module, thus influencing the activation of VWF. This research contributes to understanding the mechanical regulation of VWF and its potential applications.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Kayleigh M. Voos, Wenpeng Cao, Nicholas A. Arce, Emily R. Legan, Yingchun Wang, Asif Shajahan, Parastoo Azadi, Pete Lollar, Xiaohui Frank Zhang, Renhao Li
Summary: Desialylation of O-glycans around A1 increases its activity by destabilizing the AIM, leading to enhanced binding activity and platelet aggregation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Multidisciplinary Sciences
Aaron Blanchard, J. Dale Combs, Joshua M. Brockman, Anna V. Kellner, Roxanne Glazier, Hanquan Su, Rachel L. Bender, Alisina S. Bazrafshan, Wenchun Chen, M. Edward Quach, Renhao Li, Alexa L. Mattheyses, Khalid Salaita
Summary: The article introduces a nucleic acid-based molecular tension probe and molecular force microscopy (MFM) technology, which use fluorescence polarization to map the direction of pN forces applied by receptors. By utilizing structured illumination microscopy (SIM), super-resolution MFM is achieved, generating high-resolution maps of both the magnitude and orientation of pN traction forces applied by cells.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Jasmine Ito, Wallace Hunter Baldwin, Courtney Cox, John F. Healey, Ernest T. Parker, Emily R. Legan, Renhao Li, Surinder Gill, Glaivy Batsuli
Summary: This study evaluated the impact of site-specific N-linked glycan removal on FVIII properties, cell internalization, and antibody responses. The results showed that modifying FVIII N-linked glycans reduced endocytosis by dendritic cells and binding of specific antibodies, but did not significantly affect inhibitor formation in hemophilia A mice.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Wenchun Chen, Moriah S. Wilson, Yingchun Wang, Wolfgang Bergmeier, Francois Lanza, Renhao Li
Summary: This study investigated the role of RAM.1 antibody in platelet clearance mediated by trigger sequence exposure. The results showed that RAM.1 can attenuate platelet clearance and prolong platelet lifespan, providing key evidence for the causative link between trigger sequence exposure and accelerated platelet clearance. This suggests the potential therapeutic development of a RAM.1 derivative for treating GPIb-IX-mediated thrombocytopenia.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Editorial Material
Cell Biology
Renhao Li
Article
Hematology
Nicholas A. Arce, Yi Liu, Wenchun Chen, X. Frank Zhang, Renhao Li
Summary: This study aimed to determine and characterize the autoinhibitory properties of mouse VWF. The results showed that recombinant mouse AIM-A1 binds with higher affinity to GPIb alpha than its human counterpart. Activated A1 fragments lacking the AIM can effectively agglutinate platelets across the species barrier. The unfolding force of mouse AIM was found to be similar to the human AIM. These findings suggest that the regulation of VWF-GPIb alpha binding has been specifically tuned to work optimally in different rheological architectures, potentially due to differences in the AIM sequence.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Emily R. Legan, Yi Liu, Nicholas A. Arce, Ernest T. Parker, Pete Lollar, X. Frank Zhang, Renhao Li
Summary: Type 2B von Willebrand disease is an inherited bleeding disorder caused by point mutations in the von Willebrand factor A1 domain and autoinhibitory module, leading to enhanced binding to GPIb alpha. The severity of bleeding complications and platelet levels in patients varies depending on the underlying mutation. This study examines the thermodynamic stability, conformational dynamics, and biomechanical regulation of these mutations to understand the heterogeneity among them.
Article
Medical Laboratory Technology
Wenxin Huang, Renhao Li, Jue Zhang, Yiliang Cheng, Devi P. Ramakrishnan, Roy L. Silverstein
Summary: CD36 is a receptor for oxidized LDL and other endogenous danger signals that promotes athero-thrombotic processes. It physically associates with other transmembrane proteins and the N-terminal transmembrane domain is hypothesized to be involved in these interactions. By using peptide treatments and functional experiments, it was found that CD36 nTMD peptide decreased CD36 surface associations with tetraspanin CD9 and ameliorated pathologically important CD36 mediated responses to oxLDL.
TRANSLATIONAL RESEARCH
(2023)
Letter
Hematology
Yingchun Wang, Renhao Li
Article
Biochemical Research Methods
Rong Ma, Sk Aysha Rashid, Arventh Velusamy, Brendan R. Deal, Wenchun Chen, Brian Petrich, Renhao Li, Khalid Salaita
Summary: Tension-activated cell tagging (TaCT) is a novel method that utilizes flow cytometry to sort mechanically active cells.
Article
Engineering, Biomedical
Yuxin Duan, Fania Szlam, Yuesong Hu, Wenchun Chen, Renhao Li, Yonggang Ke, Roman Sniecinski, Khalid Salaita
Summary: A detection method utilizing Cas12a has been reported to amplify cellular traction forces and evaluate platelet dysfunction. This method enables the extraction of individualized dose-response curves for antiplatelet drugs and the screening of genes, cell-adhesion ligands, drugs, or metabolites that modulate cell mechanics.
NATURE BIOMEDICAL ENGINEERING
(2023)