Artificial Dense Granules: A Procoagulant Liposomal Formulation Modeled after Platelet Polyphosphate Storage Pools

Donovan, Alexander J.; Kalkowski, Joseph; Szymusiak, Magdalena; Wang, Canhui; Smith, Stephanie A.; Klie, Robert F.; Morrissey, James H.; Liu, Ying

doi:10.1021/acs.biomac.6b00577

Cited by 25 publications

(24 citation statements)

References 68 publications

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“…Platelet-derived polyP binds to Ca 2þ and Ca 2þ -polyP readily forms stable nanoparticles, suggesting that polyP mostly operates as particles on platelet surfaces rather than in soluble form in the supernatant. 32 Little is known about biosynthesis and degradation of polyP in mammalian systems. Inositol hexakisphosphate kinase 1 (IP6K1) is a key enzyme of platelet polyP biosynthe-sis.…”

Section: Inorganic Polypmentioning

confidence: 99%

Factor XII Contact Activation

Naudin

Burillo

Blankenberg

et al. 2017

Semin Thromb Hemost

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Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states.

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Section: Inorganic Polypmentioning

confidence: 99%

Factor XII Contact Activation

Naudin

Burillo

Blankenberg

et al. 2017

Semin Thromb Hemost

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“…An alternate approach to encapsulating liquids employs graphene membranes to confine the liquid, allowing the creation of vacuum‐stable nanosized liquid droplets . Although this yields much greater spatial resolution, it creates a problem for vibrational spectroscopy as graphene is a conductor.…”

mentioning

confidence: 99%

Vibrational Spectroscopy of Water with High Spatial Resolution

Jokisaari

Hachtel

et al. 2018

Advanced Materials

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The ability to examine the vibrational spectra of liquids with nanometer spatial resolution will greatly expand the potential to study liquids and liquid interfaces. In fact, the fundamental properties of water, including complexities in its phase diagram, electrochemistry, and bonding due to nanoscale confinement are current research topics. For any liquid, direct investigation of ordered liquid structures, interfacial double layers, and adsorbed species at liquid-solid interfaces are of interest. Here, a novel way of characterizing the vibrational properties of liquid water with high spatial resolution using transmission electron microscopy is reported. By encapsulating water between two sheets of boron nitride, the ability to capture vibrational spectra to quantify the structure of the liquid, its interaction with the liquid-cell surfaces, and the ability to identify isotopes including H O and D O using electron energy-loss spectroscopy is demonstrated. The electron microscope used here, equipped with a high-energy-resolution monochromator, is able to record vibrational spectra of liquids and molecules and is sensitive to surface and bulk morphological properties both at the nano- and micrometer scales. These results represent an important milestone for liquid and isotope-labeled materials characterization with high spatial resolution, combining nanoscale imaging with vibrational spectroscopy.

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“…This observation corresponds well to the biochemical principle that phosphate forms insoluble complexes with divalent metal ions 40 as well as recent reports that synthetic polyphosphate precipitates into stable spherical nanoparticles in the presence of calcium. 29,41 It is attractive to hypothesize that intracellular calcium and other divalent metal ions are stored in a (poly)phosphatecomplexed state to avoid the maintenance of steep osmolarity gradients over the phospholipid membrane of intracellular granules. Evidence from microscopy experiments supports this concept: sectioned platelets and isolated dense granules often appear as void lipid bilayers in electron microscopy studies.…”

Section: Discussionmentioning

confidence: 99%

Polyphosphate nanoparticles on the platelet surface trigger contact system activation

Verhoef

Barendrecht

Nickel

et al. 2017

Blood

120

159

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Polyphosphate is an inorganic polymer that can potentiate several interactions in the blood coagulation system. Blood platelets contain polyphosphate, and the secretion of platelet-derived polyphosphate has been associated with increased thrombus formation and activation of coagulation factor XII. However, the small polymer size of secreted platelet polyphosphate limits its capacity to activate factor XII in vitro. Thus, the mechanism by which platelet polyphosphate contributes to thrombus formation remains unclear. Using live-cell imaging, confocal and electron microscopy, we show that activated platelets retain polyphosphate on their cell surface. The apparent polymer size of membrane-associated polyphosphate largely exceeds that of secreted polyphosphate. Ultracentrifugation fractionation experiments revealed that membrane-associated platelet polyphosphate is condensed into insoluble spherical nanoparticles with divalent metal ions. In contrast to soluble polyphosphate, membrane-associated polyphosphate nanoparticles potently activate factor XII. Our findings identify membrane-associated polyphosphate in a nanoparticle state on the surface of activated platelets. We propose that these polyphosphate nanoparticles mechanistically link the procoagulant activity of platelets with the activation of coagulation factor XII.

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Artificial Dense Granules: A Procoagulant Liposomal Formulation Modeled after Platelet Polyphosphate Storage Pools

Cited by 25 publications

References 68 publications

Factor XII Contact Activation

Factor XII Contact Activation

Vibrational Spectroscopy of Water with High Spatial Resolution

Polyphosphate nanoparticles on the platelet surface trigger contact system activation

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