Fig 1.
Vesicle systems and their global dynamics.
The starting structures of the vesicle systems simulated in the study, as labeled, shown in spacefill representation with colors of different molecular species indicated inset.
Table 1.
The composition and properties of the vesicle systems.
Fig 2.
Protein aggregation and associated membrane thinning.
(A) The different configurations of OmpF association observed within Large-OmpF and DS-DL-OmpF, namely: i) tip-to-tip, ii) base-to-base, and iii) tip-to-base, corresponding to the low-energy arrangements observed in [28]. The OmpF trimers are shown in spacefill representation with the backbone and sidechain particles indicated in different colors, and schematic representations of each low-energy arrangement included inset. The percent occurrence across all trajectories is shown for each configuration. (B) Contour map representing the height of the inner leaflet of the lipid bilayer, based on the phosphate particle positions, around a cluster of OmpFs in Large-OmpF. The bilayer COM is the position of the weighted average radius of the vesicle. The same cluster of OmpFs is shown in panel (A, i). (C) Contour map representing the height of the outer leaflet of the lipid bilayer for same cluster of OmpFs in (B). (D) Contour map representing the total thickness of the bilayer for the cluster of OmpFs in (B) and (C), calculated as the distance between the phosphates of the inner and outer leaflets of the bilayer. Distances in the x and y dimensions in (B), (C) and (D) are the summed great circle distances from point to point along the edge of the grid used to group phosphate particles. Due to the 2D projection of the phosphate positions, some distortion of the area is expected towards the corners. However, the distortion is limited, as the central portion, representing only half the surface of the cube face projection, has been shown in the figure. (E) Time-dependent aggregation of OmpF. The number of occurrences of the three types of trimer-trimer interface for OmpF in Large-OmpF and DS-DL-OmpF, presented as a function of time. A cutoff distance of 6 nm between the center of mass of each OmpF subunit with every other OmpF subunit was used to determine the number of interacting subunits for each trimer.
Fig 3.
The lipid phosphate particle positions are shown relative to the weighted radial center of the bilayer in Small, Large, DS-DL-OmpF and Large-OmpF. In (B), (C), (D) and (E) the lipids are separated based on whether they are close to OmpF (< 2nm), part of the bulk lipids (≥ 2nm), or considered altogether (all). In (C) and (D), the phosphate positions are shown for each lipid type in DS-DL-OmpF. In (E), the COM of the lipids is shown for each lipid type in DS-DL-OmpF. In (F), the per frame (spaced every 20 ns) percentage of lipids close to OmpF (< 2 nm) is shown separately for DLPC and DSPC. All the distributions, (A) to (F), have been calculated from frames originating from the second half of the trajectories.
Fig 4.
Contour map indicating the relative occurrence of DLPC or DSPC lipids around an OmpF trimer in DS-DL-OmpF. The data are averaged over the final 200 ns of the trajectory. The distribution of lipids has been calculated separately for two isolated OmpF trimers, shown in (A) and (B), from the DS-DL-OmpF vesicle. Neither of the OmpF trimers interacted with any other protein during the simulations. The scale shows the relative frequency of finding either DSPC or DLPC at different positions around the OmpF trimer. The outer and inner leaflets are shown separately. Distances in the x and y dimensions are the summed great circle distances from point to point along the edge of the grid used to group phosphate particles. Due to the 2D projection of the phosphate positions, some distortion of the area is expected towards the corners. However, the distortion is limited, as the central portion, representing only half the surface of the cube face projection, has been shown in the figure.
Fig 5.
Protein aggregate associated lipid sorting.
(A) i) The direction correlation of lipid and protein displacements as a function of distance from the proteins after 0.2 ns or 2.0 ns time jumps. The data have been averaged for all proteins and over the full length of the trajectories. The correlations are shown separately for DLPC and DSPC lipids; ii) The direction correlation of phospholipids (DLPC and DSPC) and OmpF displacements for time jumps of 20 ns or 200 ns are shown as a function of the phospholipid distance from the surface of the protein. The correlation was calculated as an average over all lipids and protein movements over the course of the trajectories. Fewer data points exist for longer time jumps, leading to incomplete convergence of the correlation measure. (B) Schematic description of the calculation of the direction correlation. The direction correlation is related to the angle between the axes of rotation of two lipids, red (n1) and blue (n2), traveling on great circles, (i). In the opposite direction of travel (ii), the axis of rotation is negative, (-n1). The dot product of the two axes of rotation vectors yields cos(θ), the measure of direction correlation (see Methods section for full details of the calculation).
Fig 6.
Spherical harmonics analysis to characterize global modes of undulation in each system.
(A) The standard deviations of the fitted spherical harmonic across the trajectory, where l represents the degree and m the order. (B) The autocorrelation of the fitted spherical harmonics coefficients as a function of time for each vesicle, Small, Large, Large-OmpF and DS-DL-OmpF. The coefficients of each order (-l≤m≤l) of degree (l = 0,1,2,3) are shown in the same color but are presented as separate lines. The data presented in (A) and (B) has been obtained from frames spanning the whole trajectory.