IFAC PapersOnLine 51-19 (2018) 114–115 ScienceDirect Available online at www.sciencedirect.com 2405-8963 © 2018, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved. Peer review under responsibility of International Federation of Automatic Control. 10.1016/j.ifacol.2018.09.016 © 2018, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved. 1. INTRODUCTION Theories of the coagulation cascade have been around for decades, and they have greatly expanded in functional detail over the past several years (Qiu et al. (2014)). However, there still exists a void in the literature on the quantification of the micro-scale contribution of individual blood cell mechanics on macro-scale behaviors. We begin to bridge the trans-scale gap by modeling the cell-scale phenomena of activated platelets during coagulation. Though far less numerous than red blood cells in circu- lation, platelets play a critical role in the mechanics of coagulation (Rivera et al. (2009)). As the first responders to a bleeding event, platelets activate and their membrane receptors undergo conformational changes that facilitate the formation of small aggregate plugs. The exposure to stiffer substrates increases the number of activated mem- brane receptors resulting in an increase in the degree of platelet activation and adhesive capacity (Qiu et al. (2014)). Since platelets are the building blocks of clots, accurately capturing the mechanics of platelet interactions is critical to a meaningful multi-scale model of coagulation. 2. METHODS We implement a DEM-based model to capture the phe- nomenological cell-scale behavior of platelet-platelet and platelet-fibrin interactions. The adhesive properties ob- served by activated platelets in experimental isolated- platelet studies can be modeled by including implicit ⋆ Financial support for this work is provided by the US Depart- ment of Education Graduate Assistance in Areas of National Need fellowship program (P200A120195, P200A150050). membrane-surface mediators of various lengths defined by concentric spheres about the in silico platelets, shown schematically in Fig. 1. Each mediator length represents a collection of platelet membrane receptors. mediator platelet I II III IV Fig. 1. Schematic of the four simulated platelet mediator lengths defined by concentric spheres. We use the experimental force-distance curves obtained by Nguyen et al. (2016) in a study of platelet-platelet bond rupture at three activation levels, including non-/weakly- activated (W), partially-activated (P), and activated (A) to define the adhesive contribution from the mediators within each concentric sphere. We use a similar study to obtain platelet-fibrin rupture information and define an additional, fully-activated (F), level (Lam et al. (2011)). To implement the four levels of platelet activation in silico, we introduce an implicit spring between a platelet and an adherent substrate. The spring force for an activation level is mathematically defined by a piecewise linear function, shown in equation (1), where x is the distance between two adherent particles and the Boolean conditions correspond Keywords: blood, coagulation, platelets, cell-scale, discrete element method (DEM). Abstract: Platelets play a critical role in the mechanics and dynamics of blood clots, but the exact contribution of individual platelets on the macro-scale mechanics of whole clots is not fully understood. To elucidate the trans-scale relationship, we have developed a discrete element method (DEM)-based model of platelet-platelet and platelet-fibrin interactions that captures the adhesive capacity acquired by platelets upon activation during coagulation. Our simulation results mimic available experimental data and show that platelet-fibrin bonds are nearly thirty times stronger than the strongest platelet-platelet bonds. This cell-scale platelet model sets the framework for a downstream multi-scale model of coagulation. * Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261 USA (e-mails: mpc45, jjmcc, rparker@pitt.edu). ** Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15261 USA. *** Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 USA. Megan P. Cala * Joseph J. McCarthy * Robert S. Parker *,**,*** Modeling the Adhesive Behavior of Platelets During Coagulation ⋆