Internalization

Abstract: Non-phagocytic eukaryotic cells can internalize particles <1 microm in size, encompassing pathogens, liposomes for drug delivery or lipoplexes applied in gene delivery. In the present study, we have investigated the effect of particle size on the pathway of entry and subsequent intracellular fate in non-phagocytic B16 cells, using a range of fluorescent latex beads of defined sizes (50-1000 nm). Our data reveal that particles as large as 500 nm were internalized by cells via an energy-dependent process. With an increase in size (50-500 nm), cholesterol depletion increased the efficiency of inhibition of uptake. The processing of the smaller particles was significantly perturbed upon microtubule disruption, while displaying a negligible effect on that of the 500 nm beads. Inhibitor and co-localization studies revealed that the mechanism by which the beads were internalized, and their subsequent intracellular routing, was strongly dependent on particle size. Internalization of microspheres with a diameter <200 nm involved clathrin-coated pits. With increasing size, a shift to a mechanism that relied on caveolae-mediated internalization became apparent, which became the predominant pathway of entry for particles of 500 nm in size. At these conditions, delivery to the lysosomes was no longer apparent. The data indicate that the size itself of (ligand-devoid) particles can determine the pathway of entry. The clathrin-mediated pathway of endocytosis shows an upper size limit for internalization of approx. 200 nm, and kinetic parameters may determine the almost exclusive internalization of such particles along this pathway rather than via caveolae.

Abstract: Self-determination theory (Deci & Ryan, 1985) posits that (a) people are inherently motivated to internalize the regulation of uninteresting though important activities; (b) there are two different processes through which such internalization can occur, resulting in qualitatively different styles of self-regulation; and (c) the social context influences which internalization process and regulatory style occur. The two types of internalization are introjection, which entails taking in a value or regulatory process but not accepting it as one's own, and integration, through which the regulation is assimilated with one's core sense of self. Introjection results in internally controlling regulation, whereas integration results in self-determination. An experiment supported our hypothesis that three facilitating contextual factors--namely, providing a meaningful rationale, acknowledging the behaver's feelings, and conveying choice--promote internalization, as evidenced by the subsequent self-regulation of behavior. This experiment also supported our expectation that when the social context supports self-determination, integration tends to occur, whereas when the context does not support self-determination, introjection tends to occur.