Computational model of cellular adhesion in bulk flows

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DESCRIPTION (provided by applicant): Understanding, manipulating and controlling cellular adhesion processes is crucial to developing strategies among others, to target drug delivery via the circulatory system, grow self-assembling tissue structures in bioreactors, and miniaturize biosensors for the detection of environmental bacteria. Yet, key issues in our knowledge of cell-cell adhesion under hydrodynamic shear flow conditions remain unresolved. Therefore a computational model based on the immersed boundary method is being developed by the applicants to simulate cell-cell interactions that accounts for both the molecular interactions and the response of the cell membrane to the bulk flow. The proposed construction and development of the numerical tools will be guided and validated by measurements of receptor-mediated leukocyte-Staphylococcus Aureus bacterial cell interactions under shear conditions, critical to the immune response. Staphylococcus Aureus bacterial strains are responsible for infections which may lead to devastating consequences including sepsis with multi-organ failure, endocarditis, arthritis, vertebral osteomyelitis, epidural abscess and endophthalmitis. Our computational model of a cell in a shear flow is used to simulate intercellular collisions between deformable cells. Moreover, by integrating the deformable cell model with a probablistic model of receptor-ligand binding, important biomechanical and kinetic parameters for leukocyte-S. Aureus adhesive interactions can be calculated. Incorporating realistic cellular details will enable us to better estimate the model parameters such as intercellular contact area, contact duration and compressive and tensile forces as a function of the cellular properties and hydrodynamic shear that influence cellular adhesion. The proposed studies will also provide a framework for analyzing other receptor-mediated cellular interactions that play a fundamental role n diverse processes in biotechnology and cell physiology, and will significantly advance our understanding at the interface of fluid physics, vascular biology and nano-scale molecular interactions.