A number of arylamides have been synthesized and found to exhibit potent antimicrobial activities against a broad spectrum of Gram-positive and Gram-negative bacteria while exhibiting low toxicity toward eukaryotic cells. These facially amphiphilic foldamers have a relatively rigid intramolecular hydrogen-bonded arylamide as a framework, which places trifluormethyl versus positively charged amino and guanidino groups along opposite faces of the elongated molecule, facilitating interactions with lipid membranes. To better understand the mechanism of action of these antimicrobial foldamers, we have investigated the lipid interaction, depth of insertion, orientation, and dynamics of an arylamide, PMX30016, using (31)P and (19)F solid-state NMR spectroscopy. Static (31)P NMR line shapes of lipid membranes with a range of compositions indicate that PMX30016 does not disrupt the lamellar order of the lipid bilayer but perturbs the lipid headgroup conformation. This headgroup perturbation, manifested as systematic (31)P chemical shift anisotropy increases, is consistent with the well documented "electrometer" effect of lipid membranes in response to the addition of positive charges to membrane surfaces. Paramagnetic relaxation enhancement experiments indicate that the arylamide inserts into the membrane-water interface, just below the headgroup region. Measurement of (19)F-(19)F dipolar couplings within each CF(3) moiety revealed that PMX30016 is oriented with the molecular plane 20 degrees and 30 degrees from the membrane normal of neutral and anionic bilayers, respectively, and the long molecular axis lies parallel to the membrane plane. Thus, this arylamide inserts into the bilayer in a knife-like fashion, consistent with previous vibrational spectroscopy results. Moreover, (19)F NMR line shapes indicate that this molecular knife undergoes fast uniaxial rotation around the bilayer normal. These results suggest that antimicrobial arylamides destabilize anionic lipid membranes primarily by altering the membrane electric potential profile, and the spinning molecular knife may additionally create transient defects in the lipid membrane. Compared to typical antimicrobial peptides, this arylamide has more subtle effects on and is less disruptive of the structure of lipid bilayers.