(A-1) Diffusion and Trapping of Particles in Mucin

Introduction:: Mucus is a biological soft material that lines the surface of the respiratory and gastrointestinal tract in mammals. Strongly viscoelastic and highly networked, mucin performs a multitude of functions in the human body, including acting as a lubricating material and serving as a physical barrier to the diffusion and transport of foreign particulates and environmental pollutants. Particles trapped or diffusing in mucus may alter the physical and chemical structures. In this talk, we explore the diffusion, trapping, and transport of sub-micron and micron-sized particles in reconstituted mucin (the primary component of mucus) and in Carboxy Methylcellulose (CMC) - a mucin-like complex fluid.


Materials and Methods:: We use single particle tracking (SPT) and multiple particle tracking (MPT) passive microrheology to probe the dynamics of tracer particles, ranging from 0.5 to 5.0 microns in diameter, in CMC solutions and in reconstituted mucin solutions mixed with various anti-caking rock dusts. Particles are recorded in solution with brightfield (for tracers of size greater than 1 micron) and fluorescence microscopy (for tracer sizes < 1 micron) and tracked using in-house MATLAB routines. We compare unloaded mucin, and also mucin solutions with three different types of embedded particulates: unmodified limestone rock dust, modified limestone, and crystalline silica. We assess particle size dependence on the diffusivity of the various-sized tracers through our solutions and explore the transient trapping of tracers for times comparable to and much longer than the diffusion times. Viscoelastic properties, and in particular, the effective viscosity of mucin and mucin/dust solutions are further explored using shear rheology.


Results, Conclusions, and Discussions:: We find that the diffusivity of sub-micron and micron-sized tracers in mucin decreases with increasing particle size, following the Stokes-Einstein relation. This inverse size dependence however breaks down for very large tracer particles. At a tracer size of 5.0 microns, the particles undergo significant trapping manifesting as sub-diffusive behavior in their mean square displacement. We also find that the quality and type of the particulate in loaded mucins determine their effective viscosity. in mucin solutions, implying the mean pore size of the mucin network is less than 5.0 microns. The effective diffusivity of 0.5 – 5.0 micron-sized tracer particles increases with the addition of anti-caking dust compared to pure mucin, in contrast to previous diffusivity measurements suggesting that embedded dust interacts and modifies the effective properties of mucin due to physicochemical interactions, as well as by possibly impacting the effective pore size. Since CMC solutions have been used as mucin substitutes in studies on fungal growth, we also used particle tracking to asses the effective viscoelastic properties and track the dispersion of particles in space and time in CMC solutions. We identify the appropriate composition of CMC required to mimic the effective viscoelastic properties of the bare mucin solution. The increases in diffusivity of tracers in mucin mixed with certain types of limestone rock dust and associated previous findings on cytotoxicity prompt further

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