The Cell Surface

de B. Kahan

The Conference "Chemical and Immunologic Approaches to the Cell Surface " was organized as a multifaceted interaction between scientists representing various disciplines impinging on membrane biology. In many instances, this broad mixture of investigators yielded quite unusual scientific associations and interesting new dimensions to old problems, as the workers came to appreciate the advances, the shortcomings, and the hurdles of each area. Structural concepts of the membrane- -the nature, orientation, and inter-relationship of components--are emerging primarily from work on erythrocytes. Our understanding of surface biology demands reconstruction from the meager, but rapidly emerging, structural information. The excitement of membrane research depends in no small part on the concept that membranes are not static crystalline structures but rather dynamic systems with variable interrelationships between multiple components and phases, reflecting external environmental and internal cellular events. Modulation of the membrane can be readily studied in systems where discrete perturbation is introduced into the surface structure by stimulation with mitogens or reactions of immunoglobulins, resulting in wide-ranging effects. Examination of sequential changes such as patching and capping, in intact cells or in artificially reconstituted lipids, or lipide-protein, membrane systems probably represent useful iatrogenic probes to mimic genuine in vivo biophysical phenomena related to the mobility, cooperatively and constraint of surface components. The concept of solubilizing membrane components represents a more aggressive approach to the biochemical study of the surface, than does the passive dependence on the analysis of naturally soluble components, such as blood group substances shed into colostrum, ovarian cyst fluid, or gastric mucus. By separating surface glycoproteins, glycolipids, lipids, and protein components from the bulk sea of lipid, solubilization has achieved some success in dissecting the chemical nature of these moieties. Increasingly sophisticated chemical analysis is being used to compare artificially solubilized derivatives with naturally shed materials, such as HL-A antigens, P2 microglobulin, and immunoglobulins of plasma, in order to understand the relevance of the products to the native state and to thereby reconstruct the interrelationships of macromolecules in the cell surface. The synthesis of such structural and analytic data may yield a better understanding of membrane function. In many cases, the study of membrane components depends upon biologic assays which represent quite different levels in the pathway from signal reception at the cell surface to target tissue reaction. In hormone research it has been possible to obtain a direct assessment of the precise functional event of reception, namely specific binding, and even measurement of the first stage of translation, such as by detecting activation of adenyl cyclase and membrane enzymes. Release of intramembrane, intracellular, or intercellular, histiotypic messages represents a third level in the hierarchy of biologic assays. Finally, the activity of some surface components can only be detected by effects on homeostatic systems at the level of the intact organism, such as the immune mechanism. In such a case, namely the assessment of histocompatibility and tumor-specific antigens, the chemist must rely upon relatively qualitative, "end - stage" assays, reflecting multiple complex factors remote from the primary specific, membrane interaction. In choosing this wide domain, the Editors are unabashed by their lack of constraint in the scope of the endeavor. They openly admit to often artificially contriving possible relationships between divergent areas,even when none were immediately apparent. The motivating force for this poetic license was the desire to obtain a wide-ranging discussion of problems, so that experiences of membrane chemists engaged in research in one area might somehow relieve the impasse being encountered in other areas . This endeavor resulted in more than a classification of common problems; the volume apposes information and a critical discussion of data in an original fashion, not even available in the widely divergent, primary source materials. The Editors are indebted to the American Cancer Society, Merck, Sharpe and Dohme, Hoffman-LaRoche, The Upjohn Company, Meloy Laboratories, Plenum Press, Armour Pharmaceutical, and ICI America for their encouragement and financial support of the conference. Mr. Eugene Wallach and his team performed far beyond their previous heights, by extending from immunology to chemistry, and yet providing an amazingly accurate, rapid transcription of the Proceedings. Ms. R. Jaekel and K. Tamm provided the final solution to the jigsaw puzzle of edited pieces, figures, and direct galley pages.The prospects for understanding structure and function in the complex, multiphasic membrane