Introduction

Platelets play a critical role in hemostasis and coagulation. At rest, they circulate in blood as small anucleated discs, measuring 3 × 0.5 µm. Following blood vessel injury and disruption of the endothelial layer, platelets avidly interact with exposed elements of the underlying connective tissue, a reaction that is further stimulated by soluble factor release. They rapidly change from discoid shapes into active forms, first by rounding, then by generating finger-like projections called filopodia and spreading over surfaces using thin sheet-like extensions called lamellipodia. A sturdy cytoskeleton composed of actin and tubulin polymers maintains the shape of the resting and activated platelet. Actin and tubulin are dynamic polymers that can be reversibly assembled. When assembled they can be crosslinked into higher-order structures such as bundles and networks, fragmented into smaller pieces, and slide relative to one another by motor proteins. A large cast of cytoskeletal-associated proteins controls these dynamic processes. Actin filament assembly, temporally and spatially, orchestrates the extension of filopodia and lamellipodia and shape transformation.

The cytoskeleton of the resting platelet

Resting platelets are discs (Fig. 6.1(a)) whose surfaces are smooth and featureless except for small membrane invaginations that mark entrances into the open canalicular system (OCS). Cytoskeletal proteins that maintain the discoid shape represent a large fraction of the platelet proteome. Actin, present at a concentration of 0.55 mM (230000 actin subunits/platelet), represents 20% of the total cellular protein.