A theory of coalescence of signaling receptor clusters in immune cells.

A theory of coalescence of signal receptor clusters in mast cells is developed in close connection with experiments. It is based on general considerations involving a feedback procedure and a time-dependent capture as part of a reaction-diffusion process. Characteristic features of observations that need to be explained are indicated and it is shown why calculations available in the literature are not satisfactory. While the latter involves static centers at which the reaction part of the phenomenon occurs, by its very nature, coalescence involves dynamically evolving centers. This is so because the process continuously modifies the size of the cluster aggregate which then proceeds to capture more material. We develop a procedure that consists of first solving a static reaction-diffusion problem and then imbuing the center with changing size. The consequence is a dependence of the size of the signal receptor cluster aggregate on time. A preliminary comparison with experiment is shown to reveal a sharp difference between theory and data. The observation indicates that the reaction occurs slowly at first and then picks up rapidly as time proceeds. Parameter modification to fit the observations cannot solve the problem. We use this observation to build into the theory an accumulation rate that is itself dependent on time. A memory representation and its physical basis are explained. The consequence is a theory that can be fit to observations successfully.

Magnetic Nanodrug Delivery Through the Mucus Layer of Air-Liquid Interface Cultured Primary Normal Human Tracheobronchial Epithelial Cells.

Superparamagnetic iron oxide (Fe3O4) and highly anisotropic barium hexaferrite (BaFe12O19) nanoparticles were coated with an anti-inflammatory drug and magnetically transported through mucus produced by primary human airway epithelial cells. Using wet planetary ball milling, dl-2-amino-3-phosphonopropionic acid-coated BaFe12O19 nano-particles (BaNPs) of 1-100 nm in diameter were prepared in water. BaNPs and conventional 20-30-nm Fe3O4 nanoparticles (FeNPs) were then encased in a polymer (PLGA) loaded with dexamethasone (Dex) and tagged for imaging. PLGA-Dex-coated BaNPs and FeNPs were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and superconducting quantum interference device (SQUID) magnetometry. Both PLGA-Dex-coated BaNPs and FeNPs were transferred to the surface of a ~100-µm thick mucus layer of air-liquid interface cultured primary normal human tracheobronchial epithelial (NHTE) cells. Within 30 min, the nanoparticles were pulled successfully through the mucus layer by a permanent neodymium magnet. The penetration time of the nanomedicine was monitored using confocal microscopy and tailored by varying the thickness of the PLGA-Dex coating around the particles.

Reaction-diffusion theory in the presence of an attractive harmonic potential.

Problems involving the capture of a moving entity by a trap occur in a variety of physical situations, the moving entity being an electron, an excitation, an atom, a molecule, a biological object such as a receptor cluster, a cell, or even an animal such as a mouse carrying an epidemic. Theoretical considerations have almost always assumed that the particle motion is translationally invariant. We study here the case when that assumption is relaxed, in that the particle is additionally subjected to a harmonic potential. This tethering to a center modifies the reaction-diffusion phenomenon. Using a Smoluchowski equation to describe the system, we carry out a study which is explicit in one dimension but can be easily extended for arbitrary dimensions. Interesting features emerge depending on the relative location of the trap, the attractive center, and the initial placement of the diffusing particle.