The macromolecular architecture of platelet-derived microparticles

Tamir, Adi; Sorrentino, Simona; Motahedeh, Sarah; Shai, Ela; Dubrovsky, Anna; Dahan, Idit; Eibauer, Matthias; Studt, Jan‐Dirk; Sapra, K. Tanuj; Varon, David; Medalia, Ohad

doi:10.1016/j.jsb.2015.12.013

Cited by 21 publications

(20 citation statements)

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“…This was also recently shown for integrins embedded in the membranes of platelet-derived microparticles. 32 Based on these results and our ongoing work, it is very likely that by applying cryo-ET the structural conformations of integrins may be resolved in situ.…”

Section: Zooming Into Intact Platelets With Cryo-electron Tomographymentioning

confidence: 77%

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Toward correlating structure and mechanics of platelets

Sorrentino

Studt

Horev

et al. 2016

Cell Adhesion & Migration

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The primary physiological function of blood platelets is to seal vascular lesions after injury and form hemostatic thrombi in order to prevent blood loss. This task relies on the formation of strong cellular-extracellular matrix interactions in the subendothelial lesions. The cytoskeleton of a platelet is key to all of its functions: its ability to spread, adhere and contract. Despite the medical significance of platelets, there is still no high-resolution structural information of their cytoskeleton. Here, we discuss and present 3-dimensional (3D) structural analysis of intact platelets by using cryoelectron tomography (cryo-ET) and atomic force microscopy (AFM). Cryo-ET provides in situ structural analysis and AFM gives stiffness maps of the platelets. In the future, combining highresolution structural and mechanical techniques will bring new understanding of how structural changes modulate platelet stiffness during activation and adhesion.

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Section: Zooming Into Intact Platelets With Cryo-electron Tomographymentioning

confidence: 77%

“…A mechanical map of an entire platelet was then recorded by force-volume (FV) imaging. Instead of 32 The black line is a Gaussian fit to the histogram.…”

Section: Mechanical Characterization Of Plateletsmentioning

confidence: 99%

Toward correlating structure and mechanics of platelets

Sorrentino

Studt

Horev

et al. 2016

Cell Adhesion & Migration

Self Cite

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“…Platelet-derived microparticles (PMPs), membrane vesicles released during platelet activation [11], were regarded as important inflammatory bodies involving many kinds of bioactive substances, some of which were inflammatory mediators that act on target cells, and were able to amplify intercellular signaling cascade and participate in the inflammatory process [12–14]. Meanwhile, the level of PMPs significantly increased in peripheral blood and synovial fluid of patients with active RA [15].…”

Section: Introductionmentioning

confidence: 99%

Modulation of platelet-derived microparticles to adhesion and motility of human rheumatoid arthritis fibroblast-like synoviocytes

et al. 2017

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Platelet-derived microparticles (PMPs) are closely associated with disease activity in rheumatoid arthritis (RA) and contribute to the inflammatory process. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play important roles in the progression of joint destruction. The aim of this study is to demonstrate whether PMPs affect the adhesion and motility of RA-FLSs. Our data indicated that PMPs promoted migration, invasion and adhesion to extracellular matrix (ECM) of RA-FLSs. Further study showed that PMPs up-regulated the expression of matrix metalloproteinase-1 (MMP1) and increased the level of phosphorylation of NF-κB (p-NF-κB) and Erk (p-Erk) in RA-FLSs. These results suggest that PMPs promote RA-FLSs adhesion and motility presumably by increasing MMP1 via activating Erk-mediated NF-κB pathway.

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“…EV levels are modulated in certain pathologies, and studies have established the vast diversity of EVs produced by cells, suggesting that EVs might be used as biomarkers27. Groups of scientists have established the most appropriate pre-analytical conditions for the study of EVs and for the design of modern methodologies for their fine characterization3910111314171826272930484950. Furthermore, efforts have been made in recent years to institute a coherent nomenclature for EVs44.…”

Section: Discussionmentioning

confidence: 99%

“…EV subpopulations may contain active proteasome, organelles ( e.g . mitochondria), and may undergo post-translational modification in disease, such as citrullination in inflammatory arthritis41623252627. Furthermore, EVs are decorated with autoantibodies in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)162328, and different platelet stimuli were shown to trigger release of different EV subpopulations1824.…”

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confidence: 99%

Revealing the diversity of extracellular vesicles using high-dimensional flow cytometry analyses

Marcoux

Duchez

Cloutier

et al. 2016

Sci Rep

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Extracellular vesicles (EV) are small membrane vesicles produced by cells upon activation and apoptosis. EVs are heterogeneous according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. Whereas it is apparent that EVs are implicated in intercellular communication, they can also be used as biomarkers. Continuous improvements in pre-analytical parameters and flow cytometry permit more efficient assessment of EVs; however, methods to more objectively distinguish EVs from cells and background, and to interpret multiple single-EV parameters are lacking. We used spanning-tree progression analysis of density-normalized events (SPADE) as a computational approach for the organization of EV subpopulations released by platelets and erythrocytes. SPADE distinguished EVs, and logically organized EVs detected by high-sensitivity flow cytofluorometry based on size estimation, granularity, mitochondrial content, and phosphatidylserine and protein receptor surface expression. Plasma EVs were organized by hierarchy, permitting appreciation of their heterogeneity. Furthermore, SPADE was used to analyze EVs present in the synovial fluid of patients with inflammatory arthritis. Its algorithm efficiently revealed subtypes of arthritic patients based on EV heterogeneity patterns. Our study reveals that computational algorithms are useful for the analysis of high-dimensional single EV data, thereby facilitating comprehension of EV functions and biomarker development.

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The macromolecular architecture of platelet-derived microparticles

Cited by 21 publications

References 50 publications

Toward correlating structure and mechanics of platelets

Toward correlating structure and mechanics of platelets

Modulation of platelet-derived microparticles to adhesion and motility of human rheumatoid arthritis fibroblast-like synoviocytes

Revealing the diversity of extracellular vesicles using high-dimensional flow cytometry analyses

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