P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane

Abstract

In response to vascular damage, P-selectin molecules are secreted onto the surface of cells that line our blood vessels. They then serve as mechanical anchors to capture leucocytes from the blood stream. Here, we track individual P-selectin molecules released at the surface of live endothelial cells following stimulated secretion. We find P-selectin initially shows fast, unrestricted diffusion but within a few minutes, movement becomes increasingly restricted and ~50% of the molecules become completely immobile; a process similar to a sol-gel transition. We find removal of the extracellular C-type lectin domain (ΔCTLD) and/or intracellular cytoplasmic tail domain (ΔCT) has additive effects on diffusive motion while disruption of the adapter complex, AP2, or removal of cell-surface heparan sulphate restores mobility of full-length P-selectin close to that of ΔCT and ΔCTLD respectively. We have found P-selectin spreads rapidly from sites of exocytosis and evenly decorates the cell surface, but then becomes less mobile and better-suited to its mechanical anchoring function.

“Shutter” Effects Enhance Protein Diffusion in Dynamic and Rigid Molecular Networks

“…We developed a shutter model, revealing the mechanism of how the molecular size and dynamic bond exchange determined the diffusion modes, including the Brownian dynamics, hopping, and restricted dynamics. In essence, such an effect is dominated by the association–dissociation states of the reversible bonds or stickers in the dynamic networks, which should be qualitatively general in supramolecular hydrogels. − Our results not only provide a novel perspective to understand the possible mechanism of enhanced diffusion behaviors in ECM but also provide guidance for the structural design of novel biomaterials for cell culture and tissue engineering applications.…”

CD44: a cancer stem cell marker and therapeutic target in leukemia treatment

“…Different types of selectins typically act at different stages of cell rolling as important molecules located in endothelial cells for interaction with CD44. For example, P-selectin is known to affect the fast roll of the prophase, while E-selectin mediates CD44 engagement during the slow rolling of neutrophils (93,94). Furthermore, in various T cell conditions, CD44 collaborates with other ligands like HA and integrins to facilitate the rolling and adhesion of T cells.…”