A multiscale model for multiple platelet aggregation in shear flow.

Area of Science:

• Biophysics
• Computational Biology
• Rheology

Background:

• Platelet aggregation is crucial for hemostasis and thrombosis.
• Understanding platelet interactions under shear flow is vital for cardiovascular research.
• Molecular mechanisms of platelet aggregation, particularly receptor-ligand interactions, require detailed investigation.

Purpose of the Study:

• To develop and validate a multiscale computational model for simulating platelet aggregation in shear flow.
• To quantify molecular-level contact characteristics and inter-platelet forces during aggregation.
• To map stress and velocity distributions on platelet membranes during aggregation events.

Main Methods:

• A multiscale model combining coarse-grained molecular dynamics (CGMD) for platelets and dissipative particle dynamics (DPD) for shear flow.
• Development of a hybrid aggregation force field to model α_IIbβ₃ receptor-fibrinogen interactions.
• Definition and application of an aggregation tensor to quantify molecular contact characteristics.

Main Results:

• Numerical simulations of platelet doublets and triplets under varying flow conditions.
• Evaluation of contact area, detaching force, and minimum inter-platelet distance.
• Quantification of applied stress and velocity magnitude distributions on platelet membranes, showing increased stress in contact regions.

Conclusions:

• The developed multiscale model dynamically quantifies platelet aggregation characteristics and stress distribution.
• The model provides in vitro-inaccessible insights into platelet mechanotransduction and flow-induced shear stress responses.
• The framework is extensible for analyzing larger platelet aggregates and their adhesive properties.