Cell surface receptors and their ligands

Internalizing Cell-Surface Receptors and Their Ligands... 

Specific interactions between the cell surface receptors and their ligands (proteins or peptides) form the basis of cell adhesion in microfluidic devices. This entry will review methods of immobilizing ligands in microfluidic devices to achieve selective cell adhesion. 

Receptors and their ligands are numerous, varied, and essential to all forms of life. Cell-surface receptors on bacteria detect feeding attractants as well as dangerous molecules. From bacteria to humans seven-helix receptors function to detect light, odors, hormones, and other molecules. Tire numbers of different receptors are impressive. For example, the tiny nematode C. elegans has 650 seven-helix transmembrane receptors and 411 protein kinases, many of which may be associated with receptors.34 Our bodies have thousands. 

Fig. 3. Levels of complexity in receptor state and location. Receptors may be unbound, bound, or coupled with other membrane-associated molecules. Receptors and their ligands may be internalized and routed through intracellular compartments. Both receptors at the cell surface and receptors inside the cell may have signaling capabilities, although these capabilities are likely to be a function of the receptor state and location.

Whether on natural or synthetic materials, cell adhesion is mediated by protein interactions with cell surface receptors. There are several classes of cell surface receptors, and this chapter will discuss integrins, selectins, and immunoglobulins. These receptors bind their ligands with high affinity and specificity, and while each receptor family regulates separate cellular functions, there is some overlap between families. Each of these receptor families possesses a characteristic molecular structure, with every receptor... 

Screening the molecular heterogeneity of receptor expression in endothelial cell surfaces is required for the development of vascular-targeted therapies. First, as opposed to targeting purified proteins as discussed above, membrane-bound receptors are more likely to preserve their functional conformation, which can be lost upon purification and immobilization outside the context of intact cells. Moreover, many cell surface receptors require the cell membrane microenvironment to function so that protein-protein interaction may occur. Finally, combinatorial approaches may allow the selection of cell membrane ligands in a functional assay and without any bias about the cellular surface receptor. Therefore, even as yet unidentified receptors may be targeted. 

The neurotrophins interact with two distinct cell surface receptor species [5,6,9] (Fig. 27-2). The neurotrophins bind to the Trk family of receptors, which serve as the principal signal transducer for this class of growth factors. The Trk receptors comprise a small, highly related family of molecules that possess an extracellular ligand binding domain that selectively interacts with the individual neurotrophin species. Trk A specifically binds NGF, TrkB interacts with BDNF and NT4/5, and TrkC preferentially binds NT3. Importantly, the Trk receptors have an intracellular tyrosine kinase domain that is activated upon neurotrophin binding. The kinase domains of the Trk family members are highly conserved and the Trks differ mainly in the structure of their extracellular domains. Trk receptor expression is limited to neurons and the... 

FIGURE 27-3 Neurotrophic cytokines and their receptors. Neurotrophic cytokines are related to IL6 and bind to cell surface receptor complexes that share a common structural organization. The four ligands interchangeably employ two distinct receptor subunits, leukemia inhibitory factor receptor 3 (LIF-Rpt) andgpl30, and some employ a ligand-specific a subunit. CNTF-R, ciliary neurotrophic factor CT-fR.cardiotrophin 1 receptor IL6-R, interleukin-6 receptor. 

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