Surface Receptors and their Ligands

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 

This lateral mobility within the membrane is important because it participates in the regulation of receptor binding to ligands. Receptor diffusivity determines the rate at which receptors can find each other, thereby determining the transport-limited rate of binding. Under purely diffusive mechanisms, the rate of receptor collision, k+ can be estimated according to the equation  

Most cellular interactions with the extracellular matrix (ECM) occur via integrins (Hynes, 2002). However, with the design of novel biomaterials in mind, the presence of other cell surface receptors such as proteoglycans and immunoglobulins may be exploited in order to create materials that elucidate a desired cellular response. Thus, while these receptor families are not typically highly involved in cell substrate binding, their existence provides the bioengineer with more possibilities to achieve alteration of cell behavior via biomaterial modification. 

Adhesive Peptide Sequences within ECM Proteins and their Receptors (For Review, 

ECM protein Adhesive peptide sequence Major receptor(s) 

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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.

Early endosomes are the main sorting station in the endocytic pathway. In their acidic interior (pH 5.9-6.0), the receptor and its ligand can be released. The receptor may be recycled to the surface by vesicles that fuse with the plasma membrane. Material that cannot escape from the early endosomes is further transported via multivesicular bodies to late endosomes and digesting lysosomes that contain a broad spectrum of peptidases and hydrolases in an acidic surrounding [for reviews on endocytosis see Refs. (10-12), for review on clathrin uptake see Refs. (9,13)]. 

For sensors, we separate the NP roles into two broad categories based upon the location of their electrochemical signal or response exo-active and core based. Exo-active surfaces describe NPs that generate an electrochemical response that occurs at the ligand-solution interface at the periphery of the NP (Fig. 11.1a). Exo-active surfaces are widely used for sensing applications due to the large number of molecular receptors and their accessibility to target molecules. 

Once inside a cell the vesicles lose their coats to become endosomes which may then fuse with lysosomes or with Golgi membranes. The removal of a clathrin coat requires ATP as well as the chaperonin Hsp 70 (Chapter 10) and a coat protein called auxilin.568 Triskelion is distorted and displaced from the clathrin cage. The interior of the newly formed endosome is quickly acidified by the action of a proton pump in the vesicle walls.554 569 This sometimes leads to dissociation of enclosed receptors from their ligands and permits recycling of receptors and lipids of the vesicle membranes to the cell surface. This is the case for the low-density lipoprotein receptor.570 571... 

The eicosanoids act in an autocrine and paracrine fashion. These ligands bind to receptors on the cell surface, and pharmacologic specificity is determined by receptor density and type on different cells. A number of the membrane receptors and their subtypes have been cloned. All of these receptors appear to be G protein-linked properties of the best-studied receptors are listed in Table 18-1. 

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