Endocytotic mechanism

The intermiceUar material exchange process can also be assisted by the exocytotic-endocytotic mechanism, i.e., through the gemmation of a minimiceUe from a miceUe, its diffusion and subsequent coalescence with another miceUe [6,69]. 

One possibility to enhance, in a controlled manner, entry of drugs into the CNS would be to alter P-glycoprotein function at the blood-brain barrier. Such an enhancement could result from (1) direct modification of export pump function by inhibitors and intracellular signals or (2) bypassing the export pump by delivery systems not being recognized as substrates (e.g., nanoparticles or vector-coupled liposomes, which are taken up by endocytotic mechanisms) [58-65],... 

An anomalously high efficacy is usually the result of the action of a protein transporter or endocytotic mechanism. Biological membranes contain protein components evolved specifically for transporting hydrophilic nutrients across the membrane. Cellular models that directly measure permeability from both passive diffusion and transport mechanisms have been developed for screening purposes using monolayers of Caco-2 intestinal adenocarcinoma cells or MDK canine kidney cells. 

While these recent studies indicate the requirement for non-receptor-mediated steps in the overall clearance pathways for triacylglycerol-rich lipoproteins, the ultimate uptake occurs by endocytotic mechanisms involving specific receptors. Studies in a variety of experimental systems predicted that the removal of chylomicron remnants occurs independent of the LDL receptor, despite the presence of apo E on these particles. Accordingly, individuals with homozygous FH, who lack functional LDL receptors, show no signs of delayed clearance of chylomicron remnants. 

The interest of PG nanogels spearheads from their nontrivial synthesis into their biological implications. For example, nanogels with sizes between 25 and 350nm have been shown to rapidly internalize into cell, with a preferred localization in the perinuclear region. As shown in Figure 6.12, there is evidence for a size-dependent endocytotic mechanism of ceU entry. In addition, such PG gel architectures afforded a safe cytotoxicity profile in the mg/ml range [27]. 

Endocytosis is essential for uptake of macromolecules and nanoparticles. Thereby, the physical and chemical characteristics of the cargo and transporter complex determine the nature of the cell uptake mechanism. Particles larger than 500 nm are typically phagocytosed or macropinocytosed, whereas smaller hydrophilic molecules are internalized by any of the various endocytotic processes [2,8]. Often, nanometersized transporter molecules or particles accomplish cell uptake simultaneously by several endocytotic mechanisms [9]. Clathrin-dependent endocytosis is the most widely understood pathway, which is present in nearly aU mammalian cells. The clathrin pathway is considered the most important uptake mechanism for several polymers such as poly(ethylene glycol)-polylactides, poly(lactide-c )-glycolide) (PLGA), silica-based nanoparticles, and chitosan nanoparticles [8, 10-12]. 

Uptake of protein by hepatocytes can occur via one of two mechanisms (a) receptor-mediated en-docytosis or (b) non-selective pinocytosis, again with subsequent protein proteolysis. Similarly, a proportion of some proteins are likely degraded within the target tissue, as binding to their functional cell surface receptors triggers endocytotic internalization of the receptor ligand complex (Figure 4.7). 

Transport mechanism Diffusion or active transport through tunneling nanotubes Diffusion or endocytotic uptake of carbon nano tubes... 

Wittrup and Belting have in several studies on CPP-mediated DNA delivery established protocols for fluorescence assisted cell sorting (FACS) analysis to obtain reliable, quantitative data on CPP-DNA complex uptake in cultured cancer cells (9). Also, procedures for co-localization studies with known markers of various endocytotic pathways using confocal microscopy are described as well as the expression of dominant negative dynamin (GTPase deficient dynamin-2) to evaluate the dynamin dependence of the uptake mechanism. The use of various drugs commonly used to disrupt endocytosis is discussed, especially with regard to their limited specificity (9). 

A protein domain similar to the ENTH-domain and contained in proteins involved in endocytotic processes. See Stahelin, R.V., Long, E, Petter, B.J. et al.. Contrasting membrane interaction mechanisms of API80 N-terminal homology (ANTH) and epsin N-terminal homology (ENTH) domains, J. Biol. Chem. 278, 28993-28999, 2003 Sun, Y., Kaksonen,... 

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