Fatty acid transport: the diffusion mechanism in model and biological membranes

The transport of fatty acids (FA) across membranes can be described by three fundamental steps: adsorption, transmembrane movement, and desorption. In model membranes, these steps are all rapid and spontaneous for most fatty acids, suggesting that FA can enter cells by free diffusion rather than by protein-mediated mechanisms. Here we present new fluorescence approaches that measure adsorption and transmembrane movement of FA independently. We show that FA adsorb to the plasma membrane of adipocytes and diffuse through the membrane by the flip-flop mechanism within the time resolution of our measurements (approximately 5 s). Thus we show that passive diffusion is a viable mechanism, although we did not evaluate its exclusivity. Important implications of the diffusion mechanism for neural cells are that all types of FA could be available and that selectivity is controlled by metabolism. Studies of FA uptake into brain endothelial cells and other brain cell types need to be performed to determine mechanisms of uptake, and metabolism of FA must be separated in order to understand the role of membrane transport in the overall uptake process.