title: Modelling of Binding Free Energy of Targeted Nanocarriers to Cell Surface.
abstract: We have developed a numerical model based on Metropolis Monte Carlo (MC) and the weighted histogram analysis method (WHAM) that enables the calculation of the absolute binding free energy between functionalized nanocarriers (NC) and endothelial cell (EC) surfaces. The binding affinities are calculated according to the free energy landscapes. The model predictions quantitatively agree with the analogous measurements of specific antibody coated NCs (100∼nm in diameter) to intracellular adhesion molecule-1 (ICAM-1) expressing EC surface inin vitrocell culture experiments. The model also enables an investigation of the effects of a broad range of parameters that include antibody surface coverage of NC, glycocalyx in bothin vivoandin vitroconditions, shear flow and NC size. Using our model we explore the effects of shear flow and reproduce the shear-enhanced binding observed in equilibrium measurements in collagen-coated tube. Furthermore, our results indicate that the bond stiffness, representing the specific antibody-antigen interaction, significantly impacts the binding affinities. The predictive success of our computational protocol represents a sound quantitative approach for model driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.
authors.affiliation: School of Mechanical and Materials Engineering, Washington State University.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania.
authors.forename: Portonovo S
authors.initials: PS
authors.lastname: Ayyaswamy
authors.affiliation: Department of Anesthesiology and Critical Care and Department of Bioengineering, University of Pennsylvania.
authors.forename: David M
authors.initials: DM
authors.lastname: Eckmann
authors.affiliation: Department of Bioengineering and Department of Chemical and Biological Engineering, University of Pennsylvania.
authors.forename: Ravi
authors.initials: R
authors.lastname: Radhakrishnan