Picoforce Method to Probe Submicroscopic Actions in Biomembrane Adhesion

Adhesive interactions are central processes in numerous biological functions like tissue assembly (development) and identification and removal of alien organisms in immune defense (Springer 1990; Takeichi 1991). It is important to recognize that the consequences of cell adhesion are more than surface bonding. For biological organisms, adhesion usually initiates signalling pathways to activate and modulate internal cell functions. These signals often lead to physical transformation of the cell interior so that it becomes more/less rigid, motive, or strongly linked to the substrate structure. Indeed, adhesion may result in complete integration of the cell interior into a macromaterial (i.e. tissue) where molecular stress-bearing linkages penetrate the cell membrane. Although the phenomenological features of cell adhesion are well recognized, little is known about the submicroscopic physical mechanisms that ultimately implement these important biological functions. Because the sites for surface bonding are sparsely distributed compared to the range of bonding forces, the actions are usually lost in a juggernaut of cell surface movements when contacts form (Evans 1994). Hence, the most common physical assay of adhesion is the strength of attachment. When intersurface bonds are very strong, the strength of attachment images the physical coupling of surface receptors to the cell membrane and cytoskeletal structure. On the other hand, if receptors are strongly anchored to the cell structure, the attachment strength may expose the receptor-ligand interaction. Thus, key questions to be addressed in physical tests of adhesion are: is adhesive strength governed by ligand-receptor bonds or linkages to cytoskeletal structure? Does receptor anchoring to the cytoskeletal structure change with binding different ligands to the receptor? What are the mechanisms involved when cells separate from substrates?