<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Role of cytoskeleton in morphological changes of\r\nblood platelets"^^ . "Platelets are an important component of blood that help maintain haemostasis. They are derived from large bone marrow residents, called megakaryocytes, which release tubular processes into the blood stream that fragment and eventually form 2 to 3 μm sized enucleate discoid platelets. Activation of platelets is caused by factors released into the bloodstream upon endothelial damage, to which they respond by undergoing a distinct order of shape transition, from discoid, to spheroid, to dendritic, and finally an extended morphology, required to form a clot. Despite the simple architecture, platelets are able to drastically alter their morphology owing to the repertoire of cytoskeletal proteins they express. Microtubules, which form a bundle running along the platelet periphery, are known to be important for maintaining the resting discoid morphology of a platelet, while actin is heavily implicated in the later stages that require adhesion. During the first step of platelet activation, the microtubule marginal band undergoes coiling, while the platelet changes from a disc to a sphere shape. Both actin and microtubules are implicated in this process but the mechanics of the process are not clearly understood. \r\n\r\nThe following project has been carried out to explore the role of cytoskeletal mechanics in triggering activation of a platelet. A combination of experimental and analysis techniques was used to quantitatively assess mechanical properties of the system in a resting state, as well as during activation, by direct measurement of the marginal band morphology. The structure and composition of the marginal band was analyzed using electron tomography, which provided detailed information on individual microtubules. Super-resolution microscopy was also used to visualize the overall morphology and composition of the marginal band. With this data we could infer the mechanical properties of the resting marginal band in fixed platelets. To analyze the dynamics of coiling process, live cell fluorescence microscopy was used in combination with a microfluidic system. With this setup, changes in the marginal band shape could be followed in response to treatment with agonists or inhibitors that affect the cytoskeleton, that is, a process analogous to mechanical perturbations of the platelet. A large population of platelets was also analyzed to infer the intrinsic variations mechanical properties of the marginal band. The Cytosim software was used to set up simulation of marginal band coiling. \r\n\r\nBy using a multifaceted approach, we were able to get novel insight into the mechanics of marginal band coiling. Firstly, we showed that length distribution of microtubules in a set of resting platelet marginal bands follows an exponential distribution. The sum of all polymerized microtubule length was found to be 101.84µm ±12.63 per platelet. The typical distance between two microtubules was found to be 30nm in a tightly packed marginal band. Secondly, by measuring the dynamics of coiling, we could infer that the marginal band behaves like a visco-elastic ring upon activation with ADP. This response was found to be dependent on actin, while thrombin activation elicited a response that manifested in an actin independent manner. Analysis of large population of platelets showed that the tubulin intensity scales as a power of five to the platelet radius, indicating a possible enrichment of tubulin in platelets. Finally, our data suggests that platelets with longer marginal bands have a higher propensity to coil. \r\n\r\nAlthough some of our results need to be followed up with further investigations, this study provides an experimental and analysis framework that allows us to quantitatively analyze platelet cytoskeleton morphology with an aim to understand the mechanics of platelet activation in healthy and disease states."^^ . "2017" . . . . . . . "Aastha"^^ . "Mathur"^^ . "Aastha Mathur"^^ . . . . . . "Role of cytoskeleton in morphological changes of\r\nblood platelets (PDF)"^^ . . . "AasthaMathur_PhD_Thesis.pdf"^^ . . . "Role of cytoskeleton in morphological changes of\r\nblood platelets (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Role of cytoskeleton in morphological changes of\r\nblood platelets (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Role of cytoskeleton in morphological changes of\r\nblood platelets (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Role of cytoskeleton in morphological changes of\r\nblood platelets (Other)"^^ . . . . . . "small.jpg"^^ . . . "Role of cytoskeleton in morphological changes of\r\nblood platelets (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #22320 \n\nRole of cytoskeleton in morphological changes of \nblood platelets\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . .