BBA 85201 # Lipid Polymorphism and the Functional Roles of Lipids in Biological Membranes P.R. Cullis and B. de Kruijff Departments of Biochemistry, University of British Columbia, Vancouver, Canada, and Institute of Molecular Biology, Rijksuniversiteit Utrecht, The Netherlands Received July 4th, 1979 ## Contents I. Introduction ..... 399 A. Functional roles of lipids in the fluid mosaic model of membranes ..... 400 B. Lipid polymorphism: Historical perspective ..... 401 II. Lipid polymorphism and experimental techniques ..... 402 III. Lipid polymorphism: Model systems ..... 403 IV. Dynamic shapes of lipids and polymorphic phase behaviour ..... 409 V. Non-bilayer lipid structures and biological membranes ..... 411 VI. Functional roles of lipids ..... 413 A. Membrane fusion ..... 413 B. Transbilayer transport ..... 414 VII. Concluding remarks ..... 417 Acknowledgements ..... 417 References ..... 417 ### I. Introduction The variety of lipids in biological membranes and their relationship to membrane function are major unsolved problems in membrane biology. The bilayer structure of biological membranes is the only major functional role of lipids that is firmly established. Observations that biological membranes contain bilayer regions and that model systems of naturally occurring and synthetic phospholipids often spontaneously adopt such a configuration on hydration provide strong evidence that the lipid component is responsible for the basic biomembrane structure. However, a single phospholipid species such as phosphatidylcholine could satisfy such structural requirements. In this context, the observation that a typical mammalian cell membrane contains one hundred or more distinctly different lipids suggests that lipids play other functional roles. In this review, we indicate alternative functional roles arising from a property of lipids that has not received the serious attention it deserves in recent years, namely the ability of lipids to adopt nonbilayer configurations in addition to the bilayer phase. This ability implies a view of biological membranes that differs from previous models such as the fluid mosaic model of Singer and Nicolson or the earlier unit membrane model. It is therefore appropriate to briefly review the possible functional roles of lipids in terms of these earlier models so that the requirement for an alternative approach becomes apparent. ### I A. Functional roles of lipids in the fluid mosaic model of membranes Within the constraints of the fluid mosaic model, it is implicit (although not explicitly stated) that the lipid component assumes a closed bilayer structure, thus realizing both a structural matrix with which functional proteins may be associated as well as an internal environment which may be regulated and controlled.BBA 85201 # Lipid Polymorphism and the Functional Roles of Lipids in Biological Membranes P.R. Cullis and B. de Kruijff Departments of Biochemistry, University of British Columbia, Vancouver, Canada, and Institute of Molecular Biology, Rijksuniversiteit Utrecht, The Netherlands Received July 4th, 1979 ## Contents I. Introduction ..... 399 A. Functional roles of lipids in the fluid mosaic model of membranes ..... 400 B. Lipid polymorphism: Historical perspective ..... 401 II. Lipid polymorphism and experimental techniques ..... 402 III. Lipid polymorphism: Model systems ..... 403 IV. Dynamic shapes of lipids and polymorphic phase behaviour ..... 409 V. Non-bilayer lipid structures and biological membranes ..... 411 VI. Functional roles of lipids ..... 413 A. Membrane fusion ..... 413 B. Transbilayer transport ..... 414 VII. Concluding remarks ..... 417 Acknowledgements ..... 417 References ..... 417 ### I. Introduction The variety of lipids in biological membranes and their relationship to membrane function are major unsolved problems in membrane biology. The bilayer structure of biological membranes is the only major functional role of lipids that is firmly established. Observations that biological membranes contain bilayer regions and that model systems of naturally occurring and synthetic phospholipids often spontaneously adopt such a configuration on hydration provide strong evidence that the lipid component is responsible for the basic biomembrane structure. However, a single phospholipid species such as phosphatidylcholine could satisfy such structural requirements. In this context, the observation that a typical mammalian cell membrane contains one hundred or more distinctly different lipids suggests that lipids play other functional roles. In this review, we indicate alternative functional roles arising from a property of lipids that has not received the serious attention it deserves in recent years, namely the ability of lipids to adopt nonbilayer configurations in addition to the bilayer phase. This ability implies a view of biological membranes that differs from previous models such as the fluid mosaic model of Singer and Nicolson or the earlier unit membrane model. It is therefore appropriate to briefly review the possible functional roles of lipids in terms of these earlier models so that the requirement for an alternative approach becomes apparent. ### I A. Functional roles of lipids in the fluid mosaic model of membranes Within the constraints of the fluid mosaic model, it is implicit (although not explicitly stated) that the lipid component assumes a closed bilayer structure, thus realizing both a structural matrix with which functional proteins may be associated as well as an internal environment which may be regulated and controlled.