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Kinetic Studies of Multivalent Nanoparticle Adhesion

  • Author(s): Wang, Mingqiu
  • Advisor(s): Haun, Jered
  • et al.

Targeted delivery of functional nanoparticles (NPs) holds tremendous potential in diagnostics and therapeutics of vascular diseases and cancer. One of the major attributes is their ability of forming multiple bonds with target cells, thereby providing the flexibility for engineering desired adhesion strength. However, the multivalent binding of nanoparticles is still poorly understood, particularly from a dynamic perspective.

In this work, we first developed Nano adhesive dynamics (NAD) simulation to investigate the binding dynamics between an antibody-conjugated, 210-nm-diameter sphere and an ICAM-1-coated surface. In the NAD simulation, the particle motions are determined using the Langevin equation and the ICAM-1-Antibody bond association and dissociation are computed using Bell's law. The NAD simulation replicated the time-decay in NP detachment rate as found in previous flow chamber assays. We found that the decreased detachment rate resulted from the heterogeneity of NPs in bonding ability, which is inherent in NP multivalence. NPs detached preferentially from those unable to quickly accumulate bonds. This could serve as a selection mechanism to eliminate NPs confined to a lower bonding ability. In addition, we found that NP detachment was driven by mechanical forces due to NP thermal motions.

In order to understand the influence of NP bonding heterogeneity on adhesion dynamics, we further examined NP detachment behaviors at higher resolutions: at sub-population level, in which we grouped NPs with similar bonding ability as in one bond potential (BP) category; and further at bond level, in which we grouped NPs with the same bond number at a time point as in one bond state. At sub-population level, we found that the whole population detachment curve from NAD simulation data could be recovered via summing up fitted detachment curves of each BP category, fitted using mixture exponential distribution with two components. At bond level, we modeled NP transition between different bond states as a birth and death process (BD process), and the transition rate matrix of BD process was parameterized from NAD simulation data. Thereby we extracted detachment rates from the transition rate matrix using first passage times to reach the detached state. Combining different levels of analysis, we were able to provide a comprehensive study on multivalent nanoparticle adhesion dynamics.

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