NEWS AND VIEWS
2 the products of either bacteria or viruses , superantigen could either reside in pan encapsulation composites. raising the obvious possibility that the creatic {3-cells or alternatively be trans With the new, site-specific binding be IDDM-associated superantigen is of in ported to the islets by infected lympho tween vesicles, the build-up of secondary fectious origin. In this regard there is cytes. Whatever the explanation, the race supramolecular structures looks to be evidence for upregulation of expression of will soon be on to identify this islet within reach, especially as the composi endogenous retroviruses in diseased pan superantigen and to determine more pre tion and thereby the distribution of bind 12 creatic {3-cells in certain mouse models , cisely its role in the aetiology of IDDM. D ing sites in vesicular systems is easily and infection with some viruses (such as controllable. And the aggregation is re congenital rubella) increases the risk H. Robson MacDonald and Hans Acha• versible: on competitive replacement of of IDDM in genetically susceptible Orbea are at the Ludwig Institute for Cancer the lipid-bound biotin, the liposome 13 individuals . As Conrad et al. point out, Research, Lausanne Branch, University of aggregates could be redispersed without the putative infectious agent encoding the Lausanne, 1066 Epalinges, Switzerland. losing the integrity of the vesicular compartments. One of us (H.R.) found MOLECULAR SELF-ASSEMBLY similar results several years ago using coloured vesicles prepared from poly diacetylene lipids with sugar headgroups. Snap-together vesicles The coloration allowed us to follow the reversible aggregation of the intact vesi Helmut Ringsdorf and Joachim Simon cles by specific binding of lectins such as 8 Concanavalin A . Chiruvolu has calcu IN cell membranes, mother nature dem far merely a variation on a theme that lated the binding forces between the onstrates the perfect interplay of mol has been extensively investigated in tethered liposomes, and found that one 3 4 5 ecular recognition and molecular self liposomes and monolayers • . Only the specific binding site between two lipo organization to assemble systems whose lipid structure and vesicle composition somes is energetically comparable to the function is based on their organization. were slightly changed. But it became very strongest binding interactions attainable 9 Science has lagged far behind. Until re interesting upon closer investigation. with nonspecific colloidal forces - but cently, attempts to use the principles of Cryo-microscopical examination of the without the disadvantages that nonspeci self-organization, regulation, replication, aggregates revealed tethered liposomes fic aggregations bring about. communication and cooper- Specific, reversible cross ativity to build up structures linking of vesicular assemblies have remained at the level of looks promising as part of ex systems such as monolayers, periments designed to examine vesicles or micellar aggregates. specific binding events and 10 Interest is growing in molecu binding forces , as the size of lar engineering of the next level I the vesicles, their degree of of supramolecular systems - functionalization or the inclu where already complex self- sion of probes can be easily 11 organized aggregates are com- controlled . Even more ex-cit bined to yield larger functional ing would be the possibility of assemblies. The aim is to mi- constructing soft biomaterials mic the fascinating pathways ; with tunable properties. Cross of nature where molecules, polymerization of the lipids, macromolecules and molec- and the use of ligand- functionalized hydrophilic po ular devices can be seen as Schematic illustration of vesicle aggregation induced by specific merely the building blocks for recognition of biotin lipids by the tetravalent protein streptavidin. lymers as cross-linking mat cells, cell complexes, organs rices, can strengthen and sta and organisms. linked to each other by biotin bilize the assembly but allow us to retain Chiruvolu et al. 1 have now combined streptavidin-biotin bridges, but which control of the bulk properties by manipu two well-known and well characterized have retained their spherical shapes and lating osmotic forces- swelling or shrink model systems, namely vesicles and seemed to have mostly unperturbed ing will influence the elastic properties of biotin-streptavidin as recognition-units. membrance surfaces. the material. Innumerable possibilities They have looked into a neglected ap In contrast, liposomes that have been exist if we can combine liposomes or plication for these systems: the formation aggregated under osmotic stress or by polymerized liposomes with polymeric 6 7 of cross-linked vesicular aggregates by addition of calcium ions · have to under materials. It will be exciting to follow site-specific recognition. go dramatic deformations to maximize the whether these concepts will finally lead to First, they prepared small unilamellar attractive forces between single vesicular artificial tissue-like composites. D vesicles from mixtures of naturally compartments. Such deformations make occurring phospholipids and biotin the vesicle membranes fragile and leaky, Helmut Ringsdorf and Joachim Simon are in functionalized lipids. Biotin (vitamin H) and sometimes lead to fusion of mem the lnstitut fUr Organische Chemie, Johan• binds to a tetravalent protein (Streptavi branes, reducing the prospect of using nes Gutenberg-Universitat, 55099 Mainz, din) from the bacterium Streptomyces assemblies of vesicles, for example as Germany. avidinii with a binding constant of ka = 15 1 10 M- . The popularity of this system 1. Chiruvolu. S. eta/. Science264, 1753-1755 (1994). 7. Hui, S. W., Nio, S., Stewart, T. P., Bani. L. T. &Huang, 2. Bayer, E. A. &Wilchek, M. (eds)Avidm-Biotin S. K. Biochem. biophys. Acta941, 130--140 originates from its widespread usage in Technology, Methods in Enzymology, Vol. 184 (1988). affinity chromatography2. Upon addition (Academic. San Diego, 1990) 8. Bader. H .. Darn, K., Hupfer, B. &Ringsdorf, H.Adv. of the tetravalent protein to the vesicular 3. Muller, w. eta/. Science262, 1706--1708 (1993). Polymer Sci. 64,1-61 (1985). 4. Ahlers, M .. Muller. W .. Reichert, A., Ringsdorf, H. & 9. lsraelachvili, J. N.lntermolecular and Surface Forces dispersion, the vesicles aggregate and Venzmer, J. Angew. Chem. 102, 1310--1327 (1990). (Academic, London, 1992). precipitate, as shown schematically in 5. McConnell, H. M., Watts, T. H., Weiss, R. M. & Brian, A. A. 10. Florin, E.. May, V. &Gaub, H. Science264, 415-417 B10chim. biophys. Acta864, 95-106 (1986). (1994). the figure. 6. Helm.C A.,lsraelachvili,J.N.&McGuiggan,P.M. 11. Gregori ad is, G. Uposome Technology, Vol. I-III (CRC, This recognition experiment is thus Biochemistry31, 1794-1805 (1992). Boca Raton, 1984). 284 NATURE • VOL 371 · 22 SEPTEMBER 1994