Nanomolar PFOA Concentrations Affect Lipid Membrane Structure: Consequences for Bioconcentration Mechanisms

Independent methods show that sub-microMolar concentrations of perfluorooctanoic acid (PFOA), a member of the PFAS family of "forever chemicals", change the properties of DPPC vesicle bilayers. Specifically, calorimetry measurements show that PFOA at concentrations as low as 0.1 nM lowers DPPC's gel-liquid crystalline transition enthalpy by several J/g without changing the transition temperature (<i>T</i>_gel-LC), and dynamic light scattering (DLS) data illustrate that PFOA markedly broadens the size distribution of DPPC vesicles. Furthermore, DLS results from PFOA-containing, DPPC vesicle solutions also contain smaller objects having diameters of 30-50 nm. Close inspection of cryo-EM images reveals that DPPC vesicles formed in the presence of PFOA are multilamellar and the smaller objects have a clear bilayer structure similar to niosomes. A consequence of these PFOA-induced changes to DPPC bilayer structure is that the bilayers themselves are more susceptible to secondary solute accumulation. Time resolved emission measurements of Coumarin 152 (C152) report that C152 is 3-fold more likely to partition into the bilayer's acyl chain, hydrophobic interior when PFOA is present, and fluorescence lifetimes from C152 partitioned into the polar region of the lipid bilayer show evidence of PFOA-induced membrane hydration below <i>T</i>_gel-LC.