Receptor at cell surfaces

The second area of growing importance is that of susceptibility to disease. It has long been known that some common diseases run in families, although it was not known why. For the same reason, known disease risk factors carry very different levels of risk for different individuals. For example, in Topic 19 we met LDL, one of the proteins associated with transport of cholesterol. This has to dock with a specific protein receptor, the LDL receptor, at cell surfaces. A variety of mutations in the gene for the LDL receptor cause familial hypercholesterolaemia affected individuals have a much enhanced risk of heart disease. Detailed study of the human genome is likely to throw up many more correlations of this kind for various kinds of cancer and other diseases. It has recently been found that a polymorphism related to survival of mediaeval plague epidemics may also be responsible for certain individuals remarkable resistance to the HIV infection that causes AIDS ... 

Certain proteins, peptides, steroids, and other small organic molecules, serve as cell messengers or mediators of signals. Hydrophilic mediators activate receptors at the surface of the target cell. Acetylcholine is a common example of such signaling molecules. It becomes bound on the exterior surface at the acetylcholine receptor of the nervous system, opening the channel. 

Fig. 16.2. The elementary processes at a chemical synapse, a) In the resting state, the nenrotrans-mitter is stored in vesicles in the presynaptic cell, b) An arriving action potential leads to influx of Ca into the presynaptic cell. Consequently, the vesicles fuse with the presynaptic membrane and the neurotransmitter is released into the synaptic cleft, c) The neurotransmitter diffuses across the synaptic cleft and binds to receptors at the surface of the postsynaptic cell. Ion channel and receptor form a structural unit. The ion channel opens and there is an influx of Na ions into the postsynaptic cell. Recychng takes place in the presynaptic cell and the vesicles are reloaded with neurotransmitter.

Evidence for Weak Field Effects at Cell Surface Receptor Sites... 

Folic acid deficient media helps up-regulating of folate receptor expression and presentation at cell surfaces (5). 

The overall rate of binding at the cell surface—which accounts for a balance between diffusion of ligand to the surface and a finite rate of association with receptors at the surface—can be calculated from the flux at the cell surface ... 

Chen et al. delivered fluorescent CdSe-ZnS QDs coated with galactoside dendrons inside HeLa, kidney, and metastatic Ixmg cancer cells, studying the trans-membrane photodynamic profiles. The more asialoprotein receptors that are present at cell surface, the more endocytosis was observed. 

Using this concept. Hammer and Lauffenburger [1987] studied the effect of external flow on cell adhesion. The cell is modeled as a solid sphere, and the receptors at the surface of the sphere are assumed to diffuse and to convect into the contact area. The main finding is that the adhesion parameters, such as the reverse and forward reaction rates and the receptor number, have a strong influence on the peeling of the cell from the substrate. 

Both oral and parenteral uptake of colloidal carrier systems have been found to depend on the nature of the carrier as such. In the latter case, the RES uptake of colloidal drug carriers depends on a number of factors, notably the surface properties of the carrier (see above). This is related to the adsorption of certain serum proteins (opsonins) at the carrier surface, which initiates various biological responses. For example, it is known that macrophages, major components in the RES system, have Fc receptors at their surfaces, which means that carriers with adsorbed IgG are more likely to be captured by these cells (52). By reducing the adsorption of the opsonins at the carrier surface, e.g. by surface treatment using PEO derivatives, a very low serum protein adsorption can be reached, thereby prolonging the bloodstream circulation time and obtaining a more uniform tissue distribution (see above). 

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