Chapter 15. Physical actions in biological adhesion
E. Evans
Departments of Pathology and Physics, University of British Columbia,
Vancouver, B.C., Canada V6T 2B5
1. Preface: Biological view of adhesion
Tissue assembly (development) and other biological functions (like identification and removal of alien organisms in immune defense) involve complex adhesive interactions. Biologists have identified and isolated many molecular 'adhesins' responsible for cellular adhesion processes [1]. Classification of receptors and ligands in cell adhesion has become a major enterprise in mammalian biology. The list is long and some of the evidence is circumstantial (e.g., 'cell sticking versus nonsticking' in relation to competitive binding of ligands to putative sites of adhesive activity). Unfortunately, little is known about the microscopic bonding actions (physical-chemical) between cell adhesion molecules. In any case, the present view of cell adhesion in biology is briefly outlined here to provide a comparative perspective for the discussion of physical actions that will follow.
The collective dogma (for mammalian cells) is that cell adhesion molecules fall into four groups.1
(i) Integrins: a family of membrane glycoproteins composed of a and b subunits. The ligand binding site is formed by both subunits; the cytoplasmic domains are thought to be connected to the cell cytoskeleton. Integrins are receptors for extracellular matrix proteins. In many instances, a specific amino acid sequence (Arg-Gly-Asp =RGD) is believed to participate in recognition [2]. Subfamilies of integrins are distinguished by their b subunits: b1 (CD29) - VLA proteins; b2 (CD18) - leukocyte integrins; and b3 (CD61) - cytoadhesins. The b1 subfamily binds to extracellular matrix proteins fibronectin, collagen, and laminin. The b2 subfamily is unique to leukocytes [3] and is thought to be important in converting circulating leukocytes to adherent tissue cells. The best characterized molecule of the b3 subfamily is glycoprotein IIb/IIIa (aIIbb3) (CD41/CD61), found exclusively on platelets and megakaryocytes. Glycoprotein IIb/IIIa plays a central role in platelet aggregation and clotting.
(ii) Selectins: another family of calcium-dependent membrane glycoproteins. To date, selectins have been found only on circulating cells and endothelium. LAM-1 (LECAM-1), expressed on neutrophils, monocytes and most lymphocytes, facilitates binding to endothelium during lymphocyte recirculation and neutrophil emigration at inflammatory sites. ELAM-1 expressed on activated endothelial cells promotes the adhesion of leukocytes. 'Rolling' attachment of leukocytes to endothelium seems to be mediated by selectins whereas 'spreading' adhesion appears to require b2 integrins LFA-1 and Mac-1 via ICAM-1 [4].
(iii) Ig superfamily: a diverse group of molecules whose structure resembles a sandwich of b-pleated sheets with disulfide bonds. The prototypical molecule is immunoglobulin. N-CAM is also a member of this superfamily [15]. Other Ig superfamily molecules function in immune response [6]. Lastly,
(iv) Cadherins: a separate family of cell adhesion molecules without structural homology to other adhesion molecules [7]. Cells in solid tissues express at least some member of the cadherin family all of which exhibit calciumdependent homophilic binding. Even though the size of the cytoplasmic domains vary greatly between these groups of cell adhesion molecules, all possess massive extracellular domains that extend prominently from the bilayer core of the membrane.
Other than for surface recognition, it is not clear why cells require a plethora of 'sticky' molecules (many types reside on the same cell) or what differences exist in physical strength of attachment amongst these 'adhesins'? One characteristic is common to all specific adhesion sites on cells: i.e. the surface density is relatively low. On the average, tens of nanometers separate adhesion sites (~ 104 lipids per site). As will be discussed, the paucity of potential attachments leads to complex mechanics of adhesion and often to catastrophic effects when adherent cells are separated.
1The author is grateful to his colleague and collaborator Dr. Susan Tha for providing the summary paraphrased in this paragraph.
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