Amino acids change solute affinity for lipid bilayers

l-Phenylalanine Partitioning Mechanisms in Model Biological Membranes

“…To evaluate the partitioning mechanisms of l -Phe, we first analyzed l -Phe’s fluorescence behavior in bulk solvents chosen to model the possible local solvation environments of a lipid bilayer vesicle: acetonitrile for a polar aprotic environment, methanol for a polar, protic environment, and cyclohexane to model the hydrophobic region created by the hydrocarbon tails. This approach has been used previously to identify changes in solvation opportunities within the membrane interior as the membrane melts. ,− One important consideration is that the region created by the lipid glycero-backbones is polar and intrinsically aprotic. Only when water begins hydrating this region is there any opportunity for hydrogen bond formation.…”

“…The calculated log P value for l -Phe is −1.4 in the uncharged, neutral phase, indicating a solubility preference for the aqueous environment rather than the organic phase. ,, However, at a biologically relevant pH (∼7.4), l -Phe is zwitterionic, and although the net charge is zero, its log P value rises to 0.12, predicting that l -Phe is just as likely to partition into a polar organic phase as remain in an aqueous phase. Initial literature reports by Chakrabarti et al predicted that only the uncharged neutralnot zwitterionicform of l -Phe permeates into the membrane and comprises only a small fraction of the total amount of l -Phe in solution. , However, more recent studies determined l -Phe in its zwitterionic form permeates deeper into the membrane allowing l -Phe monomers to be more dynamic as they interact with the lipid .…”

“…Motivated by this study, recent work in our lab studied the effects that the isomer L-Phe has on coumarin partitioning in lipid bilayer vesicles. 25 Results showed that L-Phe increased relative solute partitioning into the lipid bilayer's nonpolar region but blocked a large amount of solute from partitioning while the lipid was in the rigid and structured gel phase. 25 The calculated log P value for L-Phe is −1.4 in the uncharged, neutral phase, indicating a solubility preference for the aqueous environment rather than the organic phase.…”

“…25 Results showed that L-Phe increased relative solute partitioning into the lipid bilayer's nonpolar region but blocked a large amount of solute from partitioning while the lipid was in the rigid and structured gel phase. 25 The calculated log P value for L-Phe is −1.4 in the uncharged, neutral phase, indicating a solubility preference for the aqueous environment rather than the organic phase. 7,25,26 However, at a biologically relevant pH (∼7.4), L-Phe is zwitterionic, and although the net charge is zero, its log P value rises to 0.12, predicting that L-Phe is just as likely to partition into a polar organic phase as remain in an aqueous phase.…”

“…Using cryo-TEM, the authors proposed that Phe aggregated to form fibrils that reduced membrane rigidity, making it more permeable. Motivated by this study, recent work in our lab studied the effects that the isomer l -Phe has on coumarin partitioning in lipid bilayer vesicles . Results showed that l -Phe increased relative solute partitioning into the lipid bilayer’s nonpolar region but blocked a large amount of solute from partitioning while the lipid was in the rigid and structured gel phase …”