Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor

Deng, Wei; Xu, Yan; Chen, Wen–Chun; Paul, David S.; Syed, Anum; Dragovich, Matthew A.; Liang, Xin; Zakas, Philip M; Berndt, Michael C.; Paola, Jorge Di; Ware, Jerry; Lanza, François; Doering, Christopher B.; Bergmeier, Wolfgang; Zhang, Xiao Hui; Li, Renhao

doi:10.1038/ncomms12863

Cited by 96 publications

(178 citation statements)

References 74 publications

Supporting

Mentioning

171

Contrasting

Unclassified

Order By: Relevance

“…It should be noted that the soluble VWF-A1 used is able to bind GPIb on platelets 36 . Our results agree with the recent report that GPIb-induced platelet surface expression of CD62p requires force 28 . The low percentage shifting (<4%) of CD62p positive platelets in FACS reflects the widely accepted property of ADP as a weak agonist 29 .…”

supporting

confidence: 83%

Dual Biomembrane Force Probe Enables Single-Cell Mechanical Analysis of Signal Crosstalk between Multiple Molecular Species

Chen

et al. 2018

Biophysical Journal

View full text Add to dashboard Cite

Conventional approaches for studying receptor-mediated cell signaling, such as the western blot and flow cytometry, are limited in three aspects: 1) The perturbing preparation procedures often alter the molecules from their native state on the cell; 2) Long processing time before the final readout makes it difficult to capture transient signaling events (<1 min); 3) The experimental environments are force-free, therefore unable to visualize mechanical signals in real time. In contrast to these methods in biochemistry and cell biology that are usually population-averaged and non-real-time, here we introduce a novel single-cell based nanotool termed dual biomembrane force probe (dBFP). The dBFP provides precise controls and quantitative readouts in both mechanical and chemical terms, which is particularly suited for juxtacrine signaling and mechanosensing studies. Specifically, the dBFP allows us to analyze dual receptor crosstalk by quantifying the spatiotemporal requirements and functional consequences of the up-and down-stream signaling events. In this work, the utility and power of the dBFP has been demonstrated in four important dual receptor systems that play key roles in immunological synapse formation, shear-dependent thrombus formation, and agonist-driven blood clotting.Over the past decade, single-molecule biomechanical analyses on single cells have enabled studies of the inner workings of adhesion and signaling receptors one at a time 1 . In physiological conditions, however, multiple receptor species are present and often work cooperatively rather than independently. Understanding how multiple receptor species crosstalk to each other is essential for determining the mechanisms underlying a wide range of biological processes related to human health and diseases. One of the model receptor systems that exhibit such signaling crosstalk with other receptors is the integrin family. For example, integrin α L β 2 , or lymphocyte function-associated antigen-1 (LFA-1), crosstalks with chemokine receptors and antigen receptors via an "inside-out" signaling process 2 , which is essential for lymphocyte trafficking and immunological synapse formation 3 . The interaction between LFA-1 on a lymphocyte and its ligand, intercellular adhesion molecule-1 (ICAM-1) on an adjacent cell, can be upregulated by signals induced by binding of chemokines and antigens to their respective receptors on the same lymphocyte, manifesting enhanced cell adhesion 4,5 . As another example, upon a rapid shear force increase caused by blood flow perturbations, the function of integrin α IIb β 3 , or glycoprotein (GP) IIb-IIIa, on a platelet surface is rapidly upregulated by signals induced by ligand engagement with the mechanoreceptor GPIb 6,7 , which promotes platelet adhesion at the site of vascular injury as part of the hemostatic and thrombotic processes 8 . The synergistic binding of GPIb and GPIIb-IIIa enables efficient platelet recruitment

show abstract

supporting

confidence: 83%

Dual Biomembrane Force Probe Enables Single-Cell Mechanical Analysis of Signal Crosstalk between Multiple Molecular Species

Chen

et al. 2018

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…Under normal conditions, plasma VWF does not bind GPIbα. However, mutant VWF from patients with type 2B von Willebrand disease (VWD) exhibits heightened spontaneous binding to GPIbα and often leads to accelerated platelet clearance and thrombocytopenia 12–15 . It was recently reported that binding of type 2B VWF, or botrocetin-induced binding of wild-type VWF, to platelets under physiological shear exerts a pulling force on GPIbα and induces unfolding of the MSD therein 15 .…”

Section: Introductionmentioning

confidence: 99%

“…However, mutant VWF from patients with type 2B von Willebrand disease (VWD) exhibits heightened spontaneous binding to GPIbα and often leads to accelerated platelet clearance and thrombocytopenia 12–15 . It was recently reported that binding of type 2B VWF, or botrocetin-induced binding of wild-type VWF, to platelets under physiological shear exerts a pulling force on GPIbα and induces unfolding of the MSD therein 15 . MSD unfolding thereafter induces GPIb-IX signaling, including the elevation of intracellular Ca 2+ ([Ca 2+ ] i ), phosphatidylserine (PS) exposure and platelet desialylation, and accelerates platelet clearance 15, 16 .…”

Section: Introductionmentioning

confidence: 99%

“…It was recently reported that binding of type 2B VWF, or botrocetin-induced binding of wild-type VWF, to platelets under physiological shear exerts a pulling force on GPIbα and induces unfolding of the MSD therein 15 . MSD unfolding thereafter induces GPIb-IX signaling, including the elevation of intracellular Ca 2+ ([Ca 2+ ] i ), phosphatidylserine (PS) exposure and platelet desialylation, and accelerates platelet clearance 15, 16 . In this study we report that refrigeration-induced VWF binding to platelet GPIbα also results in shear-dependent clearance signaling events, thereby facilitating platelet clearance upon transfusion.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets

Chen

Druzak

Wang

et al. 2017

ATVB

Self Cite

View full text Add to dashboard Cite

Objective Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared upon transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed. Approach and Results Human and murine platelets were refrigerated in gas-permeable bags at 4°C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured. After refrigeration the binding of plasma VWF to platelets was drastically increased, confirming earlier studies. The binding was blocked by peptide OS1 that bound specifically to platelet glycoprotein (GP)Ibα and was absent in VWF−/− plasma. Although surface expression of GPIbα was reduced after refrigeration, refrigeration-induced VWF binding under physiological shear induced unfolding of the GPIbα mechanosensory domain on the platelet, as evidenced by increased exposure of a linear epitope therein. Refrigeration and shear treatment also induced small elevation of intracellular Ca2+, phosphatidylserine exposure and desialylation of platelets, which were absent in VWF−/− platelets or inhibited by OS1. Furthermore, refrigerated VWF−/− platelets displayed increased post-transfusion recovery and survival than wild-type ones. Similarly, adding OS1 to transgenic murine platelets expressing only human GPIbα during refrigeration improved their post-transfusion recovery and survival. Conclusions Refrigeration-induced binding of VWF to platelets facilitates their rapid clearance by inducing GPIbα-mediated signaling. Our results suggest that inhibition of the VWF-GPIbα interaction may be a potential strategy to enable refrigeration of platelets for transfusion treatment.

show abstract

“…The GPIb-IX complex detects this pulling and signals when the stalk of GPIba unfolds (see figure panel B). 5 This explained why antibodies must target the LBD of GPIba to activate and clear platelets, but did not explain why some antibodies target the GPIba LBD but cannot activate platelets. 3 Quach et al compare 2 antibodies, 6B4 and AK2, that both recognize the LBD of GPIba.…”

mentioning

confidence: 99%

Only the strong: when antibodies hold on

Thomas

2018

Blood

View full text Add to dashboard Cite

Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor

Cited by 96 publications

References 74 publications

Dual Biomembrane Force Probe Enables Single-Cell Mechanical Analysis of Signal Crosstalk between Multiple Molecular Species

Dual Biomembrane Force Probe Enables Single-Cell Mechanical Analysis of Signal Crosstalk between Multiple Molecular Species

Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets

Only the strong: when antibodies hold on

Contact Info

Product

Resources

About