title: Evolution of Multivalent Nanoparticle Adhesion via Specific Molecular Interactions.
abstract: The targeted delivery of nanoparticle carriers holds tremendous potential to transform the detection and treatment of diseases. A major attribute of nanoparticles is the ability to form multiple bonds with target cells, which greatly improves the adhesion strength. However, the multivalent binding of nanoparticles is still poorly understood, particularly from a dynamic perspective. In previous experimental work, we studied the kinetics of nanoparticle adhesion and found that the rate of detachment decreased over time. Here, we have applied the adhesive dynamics simulation framework to investigate binding dynamics between an antibody-conjugated, 200-nm-diameter sphere and an ICAM-1-coated surface on the scale of individual bonds. We found that nano adhesive dynamics (NAD) simulations could replicate the time-varying nanoparticle detachment behavior that we observed in experiments. As expected, this behavior correlated with a steady increase in mean bond number with time, but this was attributed to bond accumulation only during the first second that nanoparticles were bound. Longer-term increases in bond number instead were manifested from nanoparticle detachment serving as a selection mechanism to eliminate nanoparticles that had randomly been confined to lower bond valencies. Thus, time-dependent nanoparticle detachment reflects an evolution of the remaining nanoparticle population toward higher overall bond valency. We also found that NAD simulations precisely matched experiments whenever mechanical force loads on bonds were high enough to directly induce rupture. These mechanical forces were in excess of 300 pN and primarily arose from the Brownian motion of the nanoparticle, but we also identified a valency-dependent contribution from bonds pulling on each other. In summary, we have achieved excellent kinetic consistency between NAD simulations and experiments, which has revealed new insights into the dynamics and biophysics of multivalent nanoparticle adhesion. In future work, we will leverage the simulation as a design tool for optimizing targeted nanoparticle agents.
authors: Department of Biomedical Engineering, ‡Department of Surgery, School of Medicine, §Department of Chemical Engineering and Materials Science, ∥Chao Family Comprehensive Cancer Center, ⊥Beckman Laser Institute, and #Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine , Irvine, California 92697, United States.
authors: Mingqiu
authors: M
authors: Wang
authors: Department of Biomedical Engineering, ‡Department of Surgery, School of Medicine, §Department of Chemical Engineering and Materials Science, ∥Chao Family Comprehensive Cancer Center, ⊥Beckman Laser Institute, and #Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine , Irvine, California 92697, United States.
authors: Shreyas R
authors: SR
authors: Ravindranath
authors: Department of Biomedical Engineering, ‡Department of Surgery, School of Medicine, §Department of Chemical Engineering and Materials Science, ∥Chao Family Comprehensive Cancer Center, ⊥Beckman Laser Institute, and #Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine , Irvine, California 92697, United States.
authors: Maha K
authors: MK
authors: Rahim
authors: Department of Biomedical Engineering, ‡Department of Surgery, School of Medicine, §Department of Chemical Engineering and Materials Science, ∥Chao Family Comprehensive Cancer Center, ⊥Beckman Laser Institute, and #Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine , Irvine, California 92697, United States.
authors: Elliot L
authors: EL
authors: Botvinick
authors: Department of Biomedical Engineering, ‡Department of Surgery, School of Medicine, §Department of Chemical Engineering and Materials Science, ∥Chao Family Comprehensive Cancer Center, ⊥Beckman Laser Institute, and #Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine , Irvine, California 92697, United States.
authors: Jered B
authors: JB
authors: Haun
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D001703:Biophysics; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry*; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000906:Antibodies; D018799:Intercellular Adhesion Molecule-1