Cell surface receptors, biomaterials

A. K. Gupta and A. S. Curtis Lactoferrin and ceruloplasmin derivatized superparamagnetic iron oxide nanoparticles for targeting cell surface receptors. Biomaterials, 25,3029-3040 (2004). 

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. 

Integtins are a large family of cell surface receptors and a major specific system to promote cell adhesion to the ECM or biomaterials. All integrin receptors are composed of two non-covalently linked, heterodimeric a and (3 glycoprotein subunits. 

Specific domains of proteins (for example, those mentioned in the section Organic Phase ) adsorbed to biomaterial surfaces interact with select cell membrane receptors (Fig. 8) accessibility of adhesive domains (such as specific amino acid sequences) of select adsorbed proteins may either enhance or inhibit subsequent cell (such as osteoblast) attachment (Schakenraad, 1996). Several studies have provided evidence that properties (such as chemistry, charge, and topography) of biomaterial surfaces dictate select interactions (such as type, concentration, and conformation or bioactivity) of plasma proteins (Sinha and Tuan, 1996 Horbett, 1993 Horbett, 1996 Brunette, 1988 Davies, 1988 Luck et al., 1998 Curtis and Wilkinson, 1997). Albumin has been the protein of choice in protein-adsorption investigations because of availability, low cost (compared to other proteins contained in serum), and, most importantly, well-documented conformation or bioactive structure (Horbett, 1993) recently, however, a number of research groups have started to examine protein (such as fibronectin and vitronectin) interactions with material surfaces that are more pertinent to subsequent cell adhesion (Luck et al., 1998 Degasne et al., 1999 Dalton et al., 1995 Lopes et al., 1999). 

The studies of protein adsorption to biomaterials undertaken so far have shown that the process is understandable in terms of the principles of surface activity, mass action, surface chemistry, and transitions in the structure of proteins. Furthermore, cells with receptors for certain of the adsorbed proteins are likely to respond to surfaces in proportion to the amount of this protein on the surface, although other processes involving... 

Fig. 4.1 Mammalian cell adhesion onto a biomaterial. a Initial contact between the cell and the biomaterial conditioned with serum proteins, b Bonding between ceU surface receptors and protein adhesion Ugands. c CeU cytoskeletal reorganization with progressive ceU spreading onto the biomaterial surface. (Adapted from Ratner et al. [15])...

The surface properties of the biomaterials will determine the type, amount and conformation of the adsorbed proteins [2]. The composition of this protein layer can be different, depending on the fluid composition and adsorption time [25], Besides the composition of the protein layer, the conformation and the orientation of the protein can also change with time [8]. This conditioning protein layer will increase the cell adhesiveness, since the cells have receptors in their membranes that specifically bind to the adhesion proteins. Moreover, the protein layer also increases the cell spreading at the biomaterial surface [6,10]. 

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