NATURE|Vol 438|1 December 2005|doi:10.1038/nature04394
Membranes are more mosaic than fluid
Donald M. Engelman1 The wealth of new data on membrane protein structures and functions is changing our general view of membrane architecture. Some of the key themes that are emerging are that membranes are patchy, with segregated regions of structure and function, that lipidregions vary in thickness and composition, and that crowding and ectodomains limit exposure of lipid to the adjacent aqueous regions.
Given their biological importance, membranes have been surprisingly neglected by biochemists until recently. Perhaps this is understandable in view of the technical hurdles that working with them presents. Most methods require purification and observation inaqueous environments alien to the molecular design of a membrane, and so the field had to rely on oversimplified views that still dominate the texts and teaching in this area. But now we have a rising number of high-resolution structures, an abundance of functional data and an evolving conceptual basis for framing more pointed questions. This is leading to a great expansion of interest in the area.Articles in this Insight expose current views of the importance, findings and concepts in membrane biology in some regions of the emerging landscape. The reductionist view of biology, to which many adhere, rests in part on the structure–function hypothesis: that the structures we find are there for specific functional reasons selected by evolution. In the case of membranes, we might start with theorigin of life, noting that compartmentalization is essential for an organism, and that with compartmentalization must come specific ways to surmount the barrier defining the boundary of the compartment — the membrane. Thus, the lipid bilayer, which spontaneously forms permeability barriers surrounding aqueous interiors, must be modified by macromolecules for the uptake of nutrients and the disposalof waste. Further refinements led to the use of the barrier for its energy-storage properties and to the creation of ways to pass information between a cell and its environment. To frame a context for the reviews that follow, a few general perspectives are presented briefly below. To develop these themes fully would require a much longer text (perhaps a book?), so only representative referencesare given here, and use is made of the references in the longer treatments by the other authors.
Each of these ideas is misleading. Most of the authors of the following reviews write of the preferential associations of molecules in the membrane plane, and as an introduction I suggest that such associations are expected, that membranes are typically crowded and that their bilayers varyconsiderably in thickness. Is a membrane a random two-dimensional liquid? In the Singer–Nicholson model, molecules are distributed randomly in two dimensions. But we know from first principles and from experimental observation that non-randomness is the rule. Consider a mixture of n
Patchiness in the membrane plane
An influential step in the study of membranes was taken with the development by Singer andNicholson in 1972 of the ‘fluid mosaic model’1, which pulled together findings and ideas from the preceding decade. The model has become the standard conceptualization of membrane architecture and is shown redrawn in Fig. 1a as it appears in virtually all biochemistry texts. As important and insightful as this model has been, the emergence of new findings during the passage of 33 years hasweakened the generalizations it contains, and it is now appropriate to examine some of them more closely. The model includes the ideas that the proteins of a membrane are dispersed, are at low concentration and that they match the hydrophobic dimension of an unperturbed lipid bilayer with peripheral belts of exposed hydrophobic side chains. The lipid is seen as a sea in which mainly monomeric proteins...