## 3 Biological Mechanisms in Bacterial Adhesion as Potential Subjects of Label-Free Monitoring
### Adhesive Molecules of Bacteria and Bacterial Entry into Host Cells
#### 3.1.4 Specific Cell Receptors Involved in Cell-Cell Interaction  
A lot of adhesive factors of pathogenic bacteria recognize transmembrane cell receptors that may contribute to cell adhesion, for example, cell-cell adhesion junctions or focal contacts [17; 288]. These receptor molecules fall into four groups: the integrins, selectins, cadherins, and the immunoglobulin superfamily [289]. They have roles in mediating contact to the cytoskeleton, in the assembly of extracellular adhesion sites, and in inducing signal transduction cascades exerting major short- and long-term responses [290]. A broad range of pathogenic bacteria with various phylogenic origins bind to integrin receptors that are especially involved in cell-matrix and cell-cell interactions and are present on many cell types [291]. The integrin family comprises more than 20 transmembrane proteins. These members form a noncovalently associated heterodimer with an \(\alpha\) and a \(\beta\) subunit; 16 various \(\alpha\) and 8 various \(\beta\) variants. The extracellular regions of a particular \(\alpha\) and \(\beta\)1 chain form a specific extracellular globular head, with a ligand binding pocket that determines the substrate specificity of cells and recognizes distinct ECM ligands. The \(\alpha\) chain has multiple repeats of divalent cation-binding sites called EF-hand motif that mediate the regulation of ligand binding [17]. Generally, \(\beta\)1 integrin ligands have a sequence motif Arg-Gly-Asp (RGD) which plays an important role in integrin interaction [17; 292]. Amino acid Asp or Glu seems to be directly involved in receptor binding [293]. Many pathogens penetrate into mammalian host cells via \(\beta\)1 integrins [294]. Invasion-mediated cell entry of _Yersinia_ by \(\beta\)1 integrins is very effective [295]. In a study by [PERSON] and [PERSON] [296], the authors showed that natural ECM substrates and invasin recognize the same domain in the \(\alpha\) and \(\beta\)1 integrin chain and apply similar structural determinants. The bacterial invasin binds to integrins with greater affinity than fibronectin, a host integrin ligand [17; 297]. The activity of cytoskeletal proteins and signaling are ruled by the multimeric state of the integrin receptor [17; 298]. As invasin-promoted bacterial penetration is intensified by multimeric, it has also been speculated that invasin multimers with multiple receptor binding sites interfere with several \(\beta\)1 integrin molecules. Yersinia's YadA protein that plays role in invasion via \(\beta\)1 integrins also creates multimers in the outer membrane of bacteria [17]. Hence, these multiple ligand-receptor interactions may fixate adhesion and intensify the uptake procedure through integrins [295].  
\(\beta\)2 integrins of leukocytes also present an important entry point for pathogenic bacteria [17]. The CR3 complement receptor, the \(\alpha\)mac\(\delta\)2 integrin binds complement component C3b and mediates the entry of _Yersinia_[299], _Mycobacterium_[300], _Legionella_[301], and _Bordetella_[302]. Bacterial entry \(\alpha\)mac\(\delta\)2 integrin is performed indirectly by the deposition of complement factor C3b or by direct interaction of an adhesion with the receptor. In general, bacteria are killed in the lysosomes; however, _Legionella_ and _Mycobacterium_ survive and grow in phagocytes. Binding to integrin receptors is an essential strategy of pathogenic bacteria to interact with the cytoskeleton, trigger adhesion and penetration in a broad range of various cell types. Cadherins support Ca2+-dependent cell-cell interaction [17]. The sequence His-Ala-Val (HAV) in the first module is fixed among cadherins and is necessary for homophilic binding [17; 303]. Many more cell surface molecules have been identified that play roles in the adhesion and invasion procedures of bacteria [304].