Platelet Internalization in Early Thrombogenesis

Leistikow, Elizabeth A.

doi:10.1055/s-2007-999021

Cited by 4 publications

(4 citation statements)

References 22 publications

(30 reference statements)

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“…Platelets are exerting high contractile forces on the fibrin, so that the strain stiffening of individual fibrin fibres under tension would lead to an increase in overall network elasticity, similar to stiffening of actin networks due to tensional forces exerted by myosin filaments 29 . Also, platelets are known to reorganize network architecture and to induce additional polymerization of fibrin 1,30 . However, the contribution of these mechanisms to the enhancement of network elasticity is unclear.…”

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confidence: 99%

Mechanics and contraction dynamics of single platelets and implications for clot stiffening

et al. 2010

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Platelets interact with fibrin polymers to form blood clots at sites of vascular injury1–3. Bulk studies have shown clots to be active materials, with platelet contraction driving the retraction and stiffening of clots4. However, neither the dynamics of single-platelet contraction nor the strength and elasticity of individual platelets, both of which are important for understanding clot material properties, have been directly measured. Here we use atomic force microscopy to measure the mechanics and dynamics of single platelets. We find that platelets contract nearly instantaneously when activated by contact with fibrinogen and complete contraction within 15 min. Individual platelets can generate an average maximum contractile force of 29 nN and form adhesions stronger than 70 nN. Our measurements show that when exposed to stiffer microenvironments, platelets generated higher stall forces, which indicates that platelets may be able to contract heterogeneous clots more uniformly. The high elasticity of individual platelets, measured to be 10 kPa after contraction, combined with their high contractile forces, indicates that clots may be stiffened through direct reinforcement by platelets as well as by strain stiffening of fibrin under tension due to platelet contraction. These results show how the mechanosensitivity and mechanics of single cells can be used to dynamically alter the material properties of physiologic systems.

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confidence: 99%

Mechanics and contraction dynamics of single platelets and implications for clot stiffening

et al. 2010

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“…The first model reflects the generation of stress fiber like bundles in platelets during fibrin retraction under isometric conditions 3. Internalization of fibrin fibers is considered in another model 4. Neither model reflects in detail on the binding mode of fibrin fibers to the platelet surface, nor the separation of the initially aggregated platelets, nor the rearrangement of the contractile cytoskeleton from a constricting sphere to stress fiber like filament bundles.…”

Section: Discussionmentioning

confidence: 99%

“…3 Internalization of fibrin fibers is considered in another model. 4 Neither model reflects in detail on the binding mode of fibrin fibers to the platelet surface, nor the separation of the initially aggregated platelets, nor the rearrangement of the contractile cytoskeleton from a constricting sphere to stress fiber like filament bundles. The model proposed in the schematic drawing shown in F IGURE 8 separates the thrombin induced formation of an in vitro clot into four, fairly well distinguishable, steps: aggregation, separation, retraction, and stabilization by generating tension.…”

Section: Discussionmentioning

confidence: 99%

A New Model for in Vitro Clot Formation that Considers the Mode of the Fibrin(ogen) Contacts to Platelets and the Arrangement of the Platelet Cytoskeleton

Morgenstern

Daub

Dierichs

2001

Annals of the New York Academy of Sciences

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The constitution of platelet‐fibrin(ogen) contacts, the separation of the platelets initially aggregated, and the rearrangement of the platelet cytoskeleton during clot formation (0.5 to 60 minutes after thrombin stimulation) were investigated using ultrastructural and immunocytochemical techniques. After aggregation, fibrin polymerizing within focal contacts and from degranulating secretory granules contributed to the fibers. The initially formed focal contacts with fibrin obviously persisted during clot formation. The physiological branching of the fibers enabled separation of platelets. The contact associated cytoskeleton formed a constricting and fiber internalizing sphere, but later stress fiber like bundles. As retraction progressed, the cytoskeleton changed to stress fiber connecting focal contacts with fibers. A model of clot formation in vitro is presented that reflects both the contributions of platelets (fibrin fiber internalization and retraction) and of fibers (branching) enabling the retraction.

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“…This results in an enlargement of the OCS, a loss of its tubular shape and an increase in platelet surface area [1]. The OCS membrane contains many platelet plasma membrane proteins, such as integrins, but may sequester some proteins, presumably through internalization processes related to endocytosis [1, 2]. Since its discovery ~40 years ago, many morphological studies of OCS have been carried [3], yet it is unclear how the OCS is formed or why it is present in only some species (e.g.…”

Section: Introductionmentioning

confidence: 99%

Protein expression in platelets from six species that differ in their open canalicular system

2010

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Platelets contain an invaginated, tubular membranous structure called the surface-connected open canalicular system (SCCS or OCS), which is contiguous with the plasma membrane and serves as a site for granule fusion and as a reservoir of membrane for platelet spreading. According to ultrastructural studies, platelets from some species lack OCS. In an attempt to correlate biochemical and functional attributes with the presence of an OCS, platelets from human, mouse and dog (OCS+), and from cow, camel and horse (OCS−) were analysed for differential protein expression and aggregation in response to thrombin. Among the 18 different cytoskeletal and regulatory proteins examined, five (Rac1, RhoA, Ras, calmodulin and Src) were expressed at higher levels in OCS+ platelets (p<0.05). Given the role of Arf6 in the formation of tubular invaginations in nucleated cells, the levels of Arf6-GTP were analysed in OCS+ and OCS− platelets. There was no significant correlation between the presence of OCS and total Arf6 or Arf6-GTP levels. Comparison of platelet aggregation between different species suggests that OCS− platelets have delayed responses. This comparison of platelets from six different species, which differ in their OCS, shows the differential expression of known signaling components and foreshadows future studies focusing on OCS formation and function.

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Platelet Internalization in Early Thrombogenesis

Cited by 4 publications

References 22 publications

Mechanics and contraction dynamics of single platelets and implications for clot stiffening

Mechanics and contraction dynamics of single platelets and implications for clot stiffening

A New Model for in Vitro Clot Formation that Considers the Mode of the Fibrin(ogen) Contacts to Platelets and the Arrangement of the Platelet Cytoskeleton

Protein expression in platelets from six species that differ in their open canalicular system

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