Multiscale model of platelet translocation and collision.

The tethering of platelets on the injured vessel surface mediated by glycoprotein Ibα (GPIbα) - Von Willebrand factor (vWF) bonds, as well as the interaction between flowing platelets and adherent platelets, are two key events that take place immediately following blood vessel injury. This early-stage platelet deposition and accumulation triggers the initiation of hemostasis, a self-defensive mechanism to prevent the body from excessive blood loss. To understand and predict this complex process, one must integrate experimentally determined information on the mechanics and biochemical kinetics of participating receptors over very small time frames (1-1000 µs) and length scales (10-100 nm), to collective phenomena occurring over seconds and tens of microns.

Platelets and megakaryocytes contain functional nuclear factor-kappaB.

Objective: To investigate the presence and role of NF-kappaB proteins in megakaryocytes and platelets. The nuclear factor-kappaB (NF-kappaB) transcription factor family is well known for its role in eliciting inflammation and promoting cell survival. We discovered that human megakaryocytes and platelets express the majority of NF-kappaB family members, including the regulatory inhibitor-kappaB (I-kappaB) and I-kappa kinase (IKK) molecules.

Platelet adhesive dynamics. Part I: characterization of platelet hydrodynamic collisions and wall effects.

Abnormally high shear stresses encountered in vivo induce spontaneous activation of blood platelets and formation of aggregates, even in the absence of vascular injury. A three-dimensional multiscale computational model-platelet adhesive dynamics-is developed and applied in Part I and Part II articles to elucidate key biophysical aspects of GPIbalpha-von-Willebrand-factor-mediated interplatelet binding that characterizes the onset of shear-induced platelet aggregation. In this article, the hydrodynamic effects of the oblate spheroidal shape of platelets and proximity of a plane wall on the nature of cell-cell collisions are systematically investigated.

Platelet adhesive dynamics. Part II: high shear-induced transient aggregation via GPIbalpha-vWF-GPIbalpha bridging.

A three-dimensional multiscale computational model, platelet adhesive dynamics (PAD), is developed and applied in Part I and Part II articles to characterize and quantify key biophysical aspects of GPIbalpha-von-Willebrand-factor (vWF)-mediated interplatelet binding at high shear rates, a necessary and enabling step that initiates shear-induced platelet aggregation. In this article, an adhesive dynamics model of the transient aggregation of two unactivated platelets via GPIbalpha-vWF-GPIbalpha bridging is developed and integrated with the three-dimensional hydrodynamic flow model discussed in Part I. Platelet binding efficiencies predicted by PAD are in good agreement with platelet aggregation behavior observed experimentally, as documented in the literature.

Influence of Brownian motion on blood platelet flow behavior and adhesive dynamics near a planar wall.

We used the platelet adhesive dynamics computational method to study the influence of Brownian motion of a platelet on its flow characteristics near a surface in the creeping flow regime. Two important characterizations were done in this regard: (1) quantification of the platelet's ability to contact the surface by virtue of the Brownian forces and torques acting on it, and (2) determination of the relative importance of Brownian motion in promoting surface encounters in the presence of shear flow. We determined the Peclet number for a platelet undergoing Brownian motion in shear flow, which could be expressed as a simple linear function of height of the platelet centroid, H from the surface Pe (platelet) = .

Mechanics of transient platelet adhesion to von Willebrand factor under flow.

A primary and critical step in platelet attachment to injured vascular endothelium is the formation of reversible tether bonds between the platelet glycoprotein receptor Ibalpha and the A1 domain of surface-bound von Willebrand factor (vWF). Due to the platelet's unique ellipsoidal shape, the force mechanics involved in its tether bond formation differs significantly from that of leukocytes and other spherical cells. We have investigated the mechanics of platelet tethering to surface-immobilized vWF-A1 under hydrodynamic shear flow.