Fig. 5: Lipid polyunsaturation modulates membrane packing defects in synaptic vesicle mimics, which in turn regulates NTA-αSyn binding.

A Chemical structures of the PUFAs used in the synaptic vesicle mimics and schematics of lipid bilayers containing these PUFAs. As the degree of unsaturation increases, the tails become increasingly bulkier and exhibit increasing steric repulsion that leads to more packing defects. B Average defect area (left), defect frequency (center), and percentage coverage of the membrane surface by packing defects (right) as determined by molecular dynamics simulations. Error bars represent the SD (N = 3). C The distribution of diameters for analyzed vesicles that were incubated with 1 µM NTA-αSyn (left). Number of proteins bound to vesicles incubated with 1 µM NTA-αSyn (right). The black dashed line indicates the average values of the data sets. For each composition, a small number of vesicles were omitted from these plots as they fell below the minimum y-axis value of 5 proteins bound. The numbers of vesicles omitted are as follows: DOPC mimic (4 out of 5122 vesicles), 18:2 mimic (8 out of 5565 vesicles), 20:4 mimic (1 out of 4577 vesicles), and 22:6 mimic (29 out of 5260 vesicles). D The measured binding response of NTA-αSyn to packing defects for synaptic vesicle mimics. These binding responses correspond to the data from (B, C). The horizontal error bars are taken from (B), and the vertical error bars represent the 99% confidence interval of the mean from each composition in (C) (right). For (B), ** and *** correspond to P < 0.01 and P < 0.001, respectively, as determined by Student’s t-test. For (C), *** corresponds to P < 0.0001 as determined by unpaired Student’s t-test. The schematics in (A) are the original creations of the authors and were not generated or obtained from external sources.