Date of Award

2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemical and Biomolecular Engineering

First Advisor

John C. Crocker

Abstract

Many biological systems exhibit cell or particle adhesion to other cells and substrates through discrete multivalent ligand bridges. These systems are inherently complex as they exist at the intersection of fluid dynamics, cell-signaling pathways, reaction kinetics, and force extension response of the bridges. The interplay of these factors can lead to a range of behaviors including free advection, strong adhesion, and intermittent regimes where the particles bind transiently or roll along the surface at a nonzero velocity significantly less than the free stream velocity. Here, we study the underlying physics of such systems using a dual experimental and computational modeling approach. Experimentally, we develop a cell free microfluidic system where DNA functionalized plastic beads are perfused over a complementarily DNA functionalized glass surface. By tuning the DNA thermodynamics of the system and shear rate, we can elicit a variety of particle responses. In one instance, we use a strong binding DNA system to study the monolayer deposition of particles in a flow field, discovering that the particle-particle collision hydrodynamics play a key role in the kinetics and morphological structure of the monolayer. Then, by using more weakly binding DNA systems, we find a regime in shear rate where particles transition from strongly adhered, to rolling, to freely advecting. We then use simulations to model the rolling system and to understand the particle-to-particle variation seen in the experiments. We find that the model predicts the experimental results well, capturing not only the domain where rolling is found and the particle rolling velocity, but also the lateral diffusivity caused by the stochastic formation and rupture of DNA bridges and the distribution of rolling velocities of an individual particle. This model illuminates potential sources of particle-to-particle variation seen in the experiment, particularly in the sensitivity of rolling velocity to particle-to-wall distance. Together, these results further our understanding of adhesion through multivalent ligand binding and will help in the engineering and design of new systems.

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