IntroductionThe lateral distribution of lipids and proteins in cell membranes is known to be highly asymmetric (Edidin, 1993;Jacobson et al., 1995;Vereb et al., 2003). Elucidating how these heterogeneities are generated and maintained over relatively large distances against the randomising forces of diffusion is central to understanding many of the processes involved in cell differentiation and establishment of polarity.Uncontrolled mixing of membrane components is thought to be prevented by several complementary processes, the best known of which are interaction with the cytoskeleton, spontaneous self-association, selective internalisation and confinement behind diffusion barriers (Gumbiner and Louvard, 1985). Diffusion barriers have long been implicated in the asymmetric distribution of surface antigens, such as between the cell body and axon in neurons (Kobayashi et al., 1992), the inner and outer segments of retinal rod cells (Peters et al., 1983) and the apical and basolateral membranes in epithelial cells (Rodriguez-Boulan and Nelson, 1989), and are thought to be largely responsible for creating micrometer-sized macrodomains. Frequently, they have a physical basis in the form of electron-dense structures within the membrane, e.g. zona occludens between epithelial cells (Dragsten et al., 1981).However, confinement zones also exist at the nanometer scale. These were first suggested by low recovery rates during fluorescence photobleaching (FRAP) experiments and later demonstrated directly using laser tweezers to drag 40 nm gold particles across the cell surface (Edidin, 2003;Vereb et al., 2003). Recent work by Kusumi and co-workers (Fujiwara et al., 2002;Murase et al., 2004) using single particle tracking at very high video speeds have refined this idea into the 'picket and fence model', in which proteins and lipids are confined temporarily within 200-300 nm diameter compartments and effect long-range diffusion by 'jumping' between compartments. It is not altogether clear at present how the temporary confinement model accommodates lipid rafts, which are envisaged as dynamic structures varying in size from a few molecules to ~50 nm in diameter and are rich in cholesterol, glycosphingolipids and GPI-anchored proteins (Edidin, 2003). At all levels of scale, it seems that membrane compartments are influenced by the cytoskeleton, thereby affording a means of transducing signals from the cytoplasm to the cell surface and vice versa.The mammalian spermatozoon is an example of a polarised cell with a highly compartmentalised plasma membrane (Holt, 1984; Cardullo and Wolfe, 1990). During differentiation in the