Imaging of platelet actin nodule with high spatial and temporal resolution

Davies, Amy (2014). Imaging of platelet actin nodule with high spatial and temporal resolution. University of Birmingham. Ph.D.

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Abstract

Platelets play a critical role in haemostasis and through platelet adhesion and aggregation ensure the integrity of the cardiovascular system is maintained in the event of an injury. The actin cytoskeleton plays a pivotal role their function. However, little is known about the role of a recently characterised actin structure, the actin nodule. The aims of this thesis are to characterise the actin nodule and elucidate their role in platelet spreading. To achieve this, platelets from the Lifeact-GFP transgenic mouse are used for live-cell imaging studies which demonstrate that actin nodules are a transient, surface-proximal, stationary actin structure which requires actin polymerisation downstream of SFK activity and the presence of Arp 2/3 complex. Additionally, their co-localisation with αIIb and results from previous work suggest a role for the actin nodule in platelet adhesion. The intracellular delivery of the actin label, Lifeact, and gold nanoparticles into human platelets using pH (low) insertion peptide is investigated and successful delivery of both represents a step forward in the ability to image actin dynamics in human platelets. Additionally, functionalisation of gold nanoparticles with multiple moieties including, a luminescent europium complex, demonstrate their potential as labels for multimodal imaging of human platelet actin nodule dynamics.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):