Driven and Thermal Microparticle Rheology of Complex Biopolymer Systems

Mucociliary clearance is the process by which cilia actively transport mucus from the airway in order to keep a sterile environment in the lung. The flow properties, or the rheology, of mucus is of particular importance when considering mucus function since its modulus and viscosity result in net mucociliary transport. For example, when the protective layer of mucus is too thick, transport stops because the cilia cannot carry the increased load, as is the case in several lung-related pathologies like cystic fibrosis, COPD, and asthma. The 3DFM is an instrument we designed, implemented, and validated in our lab. Evolving significantly over the last several years, the 3DFM is a system that images and manipulates biological specimens in all three spatial dimensions at microscopic length scales. When we subject a bead embedded in a fluid to an applied force, its spatiotemporal response depends on the rheological properties of the surrounding fluid. For example, in a Newtonian fluid the terminal velocity of a bead is inversely proportional to the fluid viscosity. Applying magnetic forces to micron sized spheres or even rod-shaped particles (i.e. bacteria or magnetically permeable nanoparticles) allows us to study the correspondence (or lack thereof) between micro-physical measurements and the canonical characterizations of macroscopic rheology techniques like cone-and-plate rheometers. Also, such a microscale technique is desirable since it is often difficult to acquire sufficient volume of a purified biological sample to test using macroscale rheological techniques such as cone and plate. Biological systems can also be highly heterogeneous and present a challenge for any measurement technique because of this variability. Finally, we must mention the necessity of performing measurements at relevant length scales since evolutionary pressure is the driving force for these biopolymer systems. Here I will argue the usefulness of driven microbead rheology (DMBR) as a measurement technique for soft biopolymer solutions. I begin by explaining the effects of probe shape and make first observations regarding a preference in particle shape for drug delivery. Next, I describe the fundamental measurements in our DMBR system and offer data for well-characterized Newtonian and homogeneous viscoelastic polymer solutions. I will present experimental results and will establish the ability of DMBR as a technique for measuring both linear and nonlinear properties of non-Newtonian fluids. Finally, there will be particular attention on strain-thickening, a dynamic and nonlinear rheological property of mucus that I have observed for the first time at the microscale, making it interesting in understanding mucociliary clearance