Fatty Acid Fueled Transmembrane Chloride Transport

Generation
of chemical gradients across biological membranes of
cellular compartments is a hallmark of all living systems. Here we
report a proof-of-concept prototype transmembrane pumping system in
liposomes. The pump uses fatty acid to fuel chloride transport, thus
generating a transmembrane chloride gradient. Addition of fatty acid
to phospholipid vesicles generates a transmembrane pH gradient (pHin < pHout), and this electrochemical H+ potential is harnessed by an anionophore to drive chloride efflux
via H+/Cl– cotransport. Further addition
of fatty acid efficiently fuels the system to continuously drive chloride
transport against the concentration gradient, up to [Cl–]in 65 mM | [Cl–]out 100
mM, and is 1400 times more efficient than using an external fuel. Based
on our findings from dissecting the H+/Cl– flux process with the use of different liposomal fluorescence
assays, and supported by additional liposome-based 13C NMR and DLS studies; we proposed that the presence of an anionophore
can induce asymmetric distribution of fatty acid, and contribute to
another Cl– flux mechanism in this system.