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Fig 1.

Computational and schematic model of the APM.

(A) Computational model of the APM showing different structural components. (B) Schematic illustration of the APM based on super-resolution microscopy results of the periodic APMS structure. Ankyrin-associated Nav channels anchor the phospholipid bilayer to the membrane skeleton.

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Fig 2.

Illustration of the APM, which includes the APMS and the phospholipid bilayer.

Ankyrin G binds to the 15th repeat of β-spectrin near its carboxyl terminus and to Nav in the axon. α-spectrin and β-spectrin filaments are connected at actin junctions. It is unknown how the phospholipid bilayer is anchored at the actin rings; we indicate a generic actin-associated protein that connects the actin rings to the phospholipid bilayer. Cluster of lipids in the individual layer are represented by a particle with a diameter of 2.5 nm, which is approximately the thickness of a single phospholipid bilayer. We chose the size of TMPs and IMPs of both the inner and outer leaflets to be 5 nm when they interact with other membrane proteins and lipids. However, the IMPs of the inner leaflet and TMPs have additional components that extend towards the cytosol, whereas the IMPs of the outer leaflet do not have inner extension regions. The effective size of the IMPs of the inner leaflet and the TMPs is considered to be 20 nm and 25 nm, respectively, when they interact with the APMS.

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Fig 3.

MSDs of lipids and IMPs of the outer leaflet.

(A). 2D MSDs of lipids of inner and outer leaflets. (B). MSDs of outer leaflet IMPs in longitudinal and transversal directions. The overall MSD is the summation of longitudinal and transversal MSDs and represents surface diffusion.

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Fig 4.

MSDs and trajectories of the outer leaflet IMPs with actin-anchored proteins (AAPs) of different sizes.

(A). Longitudinal MSDs of IMPs in the outer leaflet with three sizes of AAPs. Panels (B), (C), and (D) show the trajectories of 5 nm, 15 nm, and 25 nm AAPs, respectively.

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Fig 5.

MSDs and trajectories of IMPs in the inner leaflet and TMPs.

(A). Longitudinal MSD of IMPs in the inner leaflet. (B). Trajectories of IMPs in the inner leaflet. (C). Longitudinal MSD of TMPs. (D). Trajectories of TMPs.

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Fig 6.

MSDs of the inner leaflet IMPs and TMPs along the axon’s circumferential direction.

(A). Transverse MSD of the inner leaflet IMPs at different spectrin-lipid associations. (B). Transverse MSD of TMPs at different spectrin-lipid associations.

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Fig 7.

One-dimensional MSDs of IMPs at different accumulation levels of anchored TMP.

(A). Longitudinal and (B). Transverse MSDs of IMPs of the outer leaflet at 3, 20, 45, 60 and 90 pprc. (C). Longitudinal and (D). Transverse MSDs of IMPs of the inner leaflet at 3, 20, 45, 60 and 90 pprc. The percentages of surface area coverage are 0.87%, 5.83%, 13.11%, 17.48%, and 26.22%, respectively.

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