The process of fatty acid transport across the cellular membrane occurs in three unique steps: adsorption, translocation, and desorption. The adsorption/desorption steps involve equilibrium between the membrane and surrounding media or cytosol while translocation is the movement of the fatty acid from the outer leaflet to the inner leaflet. There are essentially two competing hypotheses regarding fatty acid transport. The first is that the flip-flop of fatty acids through the hydrophobic core of the plasma membrane is the rate-limiting step to transport. In this case of prohibitively slow flip-flop, the invocation of a protein-mediated transport mechanism is necessary to support cell viability. Alternatively, the other hypothesis states the rate of fatty acid flip-flop occurs rapidly, with desorption being the rate-limiting step to transport through the membrane. This would suggest that a diffusive transport mechanism is sufficient to support the metabolic demands of the cell. The rate and mechanism by which this crossing occurs is poorly understood due to experimental difficulty of determining the rate of fatty acid flip-flop in membranes. Sum-frequency vibrational spectroscopy (SFVS) has been used to determine the rate of stearic acid (SA) flip-flop in planar-supported lipid bilayers (PSLB) composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). In addition to SA flip-flop, the effect of SA on DSPC flip-flop was also examined. SA flip-flop was found to be rapid, but surprisingly, also slows the translocation of DSPC. SFSV measurements of SA flip-flop suggest that desorption is the rate limiting step in fatty acid transport across the cellular membrane.

Fatty acid flip-flop in lipid membranes

2019 Spring National Meeting

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