Dynamic Simulations of Inflammatory Cell Recruitment: The State Diagram for Cell Adhesion Mediated by Two Receptors

White blood cell recruitment from the bloodstream to surrounding tissues is an essential component of the immune response. Capture Of hlood-borne Ieuk'Wks onto vascular endothelium proceeds via a two-step mechanism, with each step mediated by a distinct receptor-ligand pair. Cells first transiently adhere, or "roll" (via interactions between selectins and sialyl-Lewis-x), and then firmly adhere to the vascular wall (via interactions between integrins and ICAM-1). We have reported that a eomputatiokl method called Adhesive Dynamics (AD) accurately reproduces the fine scale dynamics of selectin-mediated rolling [1]. This paper extends the use of AD simulations to model the dynamics of cell adhesion when two classes of receptors are simultaneously active: one class (selectins) with weakly adhesive properties, and the other (integrins) with strongly adhesive properties. AD simulations predict synergistic functions of the two receptors in mediating adhesion. We present this relationship in a two-receptor state diagram, a map that relates the densities and properties of adhesion molecules to various adhesive behaviors that they code, such as rolling or firm adhesion. The predictions of two-receptor adhesive dynamics are validated by the ability of the model to reproduce experimental neutrophil rolling velocities. Comments Copyright 2003 IEEE. Reprinted from Proceedings of the 29th IEEE Annual Bioengineering Conference 2003, pages 158-159. Publisher URL: http://ieeexplore.ieee.org/xpl/tocresult.jsp?isNumber=27351&page=5 This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of the University of Pennsylvania's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it. This conference paper is available at ScholarlyCommons: http://repository.upenn.edu/be_papers/31 Dynamic Simulations of Inflammatory Cell Recruitment: The State Diagram for Cell Adhesion Mediated by Two ,Receptors Sujata K. Bhatia and Daniel A. Hammer Department of Bioengineering and Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA white blood cell recruitment from the bloodstream to To clarify the relationship between the molecular surrounding tissues is an essential component of the immune properties of adhesive molecules and the macroscopic response. Capture Of hlood-borne Ieuk'Wks onto vascular behavior such as rolling or fum adhesion that thev mediate. reported that a eomputatiokl method called Adhesive Dynamics (AD) accurately reproduces the fine scale dynamics of selectin-mediated rolling 111. This paper extends the use of AD simulations to model the dynamics of cell adhesion when two classes of receptors are simultaneously active: one class (selectins) with weakly adhesive properties, and the other (integrins) with strongly adhesive properties. AD simulations predict synergistic functions of the two receptors in mediating adhesion. We present this relationship in a two-receptor state diagram, a map that relates the densities and properties of adhesion molecules to various adhesive behaviors that they code, such as rolling or firm adhesion. The predictions of tworeceptor adhesive dynamics are validated by the ability of the model to reproduce experimental neutrophil rolling velocities.