Nanomolar PFOA Concentrations\nAffect Lipid Membrane\nStructure: Consequences for Bioconcentration Mechanisms

Independent methods show that sub-microMolar concentrations\nof\nperfluorooctanoic acid (PFOA), a member of the PFAS family of “forever\nchemicals”, change the properties of DPPC vesicle bilayers.\nSpecifically, calorimetry measurements show that PFOA at concentrations\nas low as 0.1 nM lowers DPPC’s gel–liquid crystalline\ntransition enthalpy by several J/g without changing the transition\ntemperature (<i>T</i><sub>gel‑LC</sub>), and dynamic\nlight scattering (DLS) data illustrate that PFOA markedly broadens\nthe size distribution of DPPC vesicles. Furthermore, DLS results from\nPFOA-containing, DPPC vesicle solutions also contain smaller objects\nhaving diameters of 30–50 nm. Close inspection of cryo-EM images\nreveals that DPPC vesicles formed in the presence of PFOA are multilamellar\nand the smaller objects have a clear bilayer structure similar to\nniosomes. A consequence of these PFOA-induced changes to DPPC bilayer\nstructure is that the bilayers themselves are more susceptible to\nsecondary solute accumulation. Time resolved emission measurements\nof Coumarin 152 (C152) report that C152 is 3-fold more likely to partition\ninto the bilayer’s acyl chain, hydrophobic interior when PFOA\nis present, and fluorescence lifetimes from C152 partitioned into\nthe polar region of the lipid bilayer show evidence of PFOA-induced\nmembrane hydration below <i>T</i><sub>gel‑LC</sub>.