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The understanding of how receptors accumulate within the developing synapse has captured a lot of attention. Lateral diffusion of surface neurotransmitter receptors has emerged as a key pathway to regulate receptor trafficking and surface distribution, in addition to the receptor cycling between intracellular and plasma membrane pools. The neurotransmitter receptor lateral diffusion depends on several factors, such as interactions with other proteins highly enriched within the synaptic structure. During synaptogenesis, receptors aggregate and cluster within developing synapses. As described in this chapter, lateral diffusion of receptors is likely to play an important role in such process since receptor lateral diffusion is high during synaptogenesis, providing favourable conditions for the “capture” of receptors within synaptic contacts. Indeed, the “diffusion-trap” model for receptor accumulation in developing synapses has now gained experimental support from excitatory synapses, although direct evidence to test this model is still lacking due to the absence of adequate tools to precisely control extrasynaptic receptor lateral diffusion. Within the developing synapse, it also emerges that neurotransmitter release generates surface instability of the receptors and their stabilization requires additional factors.

Surface structure transitions are described and shown to take place as a function of deposition rate. This behavior is seen to occur as a result of two competing time scales, one determined by the deposition rate, and the other by the rate of lateral diffusion. Discussion is given of the physical mechanism behind this effect, and its relation to non-equi1ibrium roughening.

Fluorescence is one of the most widely used spectroscopic techniques in the research of various biological phenomena; owing to its sensitivity and specificity, it has solved problems that otherwise would have been extremely difficult to approach. Especially in membrane research, fluorescence spectroscopy has become very popular. A variety of probes have been used in this field (Lacowicz, 1983), and the fluorescent phospholipid analogues are among the most promising ones. They have been used to investigate phenomena such as lateral diffusion and dynamics of lipids (Galla and Hartman, 1980; Pugh et al., 1982; Jones and Lentz, 1986), lateral distribution of lipids (Welti and Silbert, 1982; Welti, 1982; Somerharju et al., 1985; Wiener et al.,1985; Hresko et al., 1987), transbilayer movement (Homan and Pownall, 1988), phase transitions (Sklar et al., 1977), and lipid-protein interactions (Jones and Lenz, 1986; Mustonen et al.,1987). Moreover, these fluorescent probes are very useful in studies of the spontaneous (Roseman and Thompson, 1980; Massey et al., 1982; Frank et al., 1983; Arvinte and Hildenbrand, 1984; Nichols, 1987, 1988) and protein-mediated (Somerharju et al.,1981, 1983, 1987; Somerharju and Wirtz, 1982; Nichols and Pagano, 1983; Massey et al., 1985; van Paridon et al.,1987a, 1988a) transfer of phospholipids.

The effects of membrane protein density, temperature, and aqueous sucrose concentration on the maximum rate of mitochondrial electron transport and diffusion rates of redox components are examined. It is shown that these factors affect both the rate of lateral diffusion and the rate of electron transport. These effects are discussed in relation to the random collision model of mitochondrial electron transport. The results show that mitochondrial electron transport is a multicollision,obstructed, long-range, diffusional process and that the maximum rate of mitochondrial electron transport in the ubiquinone region is limited by diffusion.

The experimental implementation of a computer-based spectroscopic instrument is presented. The design is primarily aimed at the measurement of the lateral diffusion coefficient of labelled molecules. It can be used in the Fluorescence Correlation Spectroscopy mode. This approach has been presented at another lecture in this summer school.

Ubiquinone holds a central position in the mitochondrial electron transfer chain.1 The majority of mitochondrial ubiquinone is dissolved in the lipid bilayer, constituting a functionally homogeneous pool, whereas an aliquot is bound to the respiratory complexes.2 The most widely accepted organization of the respiratory chain is depicted in a random collisional model3 of the complexes and their connecting substrates (ubiquinone and cytochrome c),whereby electron transfer between dehydrogenases and the bc1 complex is assured by the lateral diffusion of the ubiquinone pool in the lipid bilayer,according to a kinetic behavior first described by Kroger and Klingenberg4 (the so-called “pool equation”).In this model,the role of bound ubiquinone molecules would be confined to the electron transfer mechanisms within the individual complexes.