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. 2016 May 10;110(9):2066-75.
doi: 10.1016/j.bpj.2016.03.013.

Steric Effects Induce Geometric Remodeling of Actin Bundles in Filopodia

Ulrich Dobramysl  1 , Garegin A Papoian  2 , Radek Erban  3
Affiliations

Steric Effects Induce Geometric Remodeling of Actin Bundles in Filopodia

Ulrich Dobramysl et al. Biophys J. .

Abstract

Filopodia are ubiquitous fingerlike protrusions, spawned by many eukaryotic cells, to probe and interact with their environments. Polymerization dynamics of actin filaments, comprising the structural core of filopodia, largely determine their instantaneous lengths and overall lifetimes. The polymerization reactions at the filopodial tip require transport of G-actin, which enter the filopodial tube from the filopodial base and diffuse toward the filament barbed ends near the tip. Actin filaments are mechanically coupled into a tight bundle by cross-linker proteins. Interestingly, many of these proteins are relatively short, restricting the free diffusion of cytosolic G-actin throughout the bundle and, in particular, its penetration into the bundle core. To investigate the effect of steric restrictions on G-actin diffusion by the porous structure of filopodial actin filament bundle, we used a particle-based stochastic simulation approach. We discovered that excluded volume interactions result in partial and then full collapse of central filaments in the bundle, leading to a hollowed-out structure. The latter may further collapse radially due to the activity of cross-linking proteins, hence producing conical-shaped filament bundles. Interestingly, electron microscopy experiments on mature filopodia indeed frequently reveal actin bundles that are narrow at the tip and wider at the base. Overall, our work demonstrates that excluded volume effects in the context of reaction-diffusion processes in porous networks may lead to unexpected geometric growth patterns and complicated, history-dependent dynamics of intermediate metastable configurations.

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Figures

Figure 1
Figure 1
Rendering of an actin filament bundle inside a filopodium. The filaments are shown in the middle, with diffusing G-actin monomers displayed around them. The gray region indicates the volume enclosed by the membrane in our model. The filament height and G-actin position data stem from an example simulation run. Filament and G-actin structure data were taken from the PDBe database (63, 64) To see this figure in color, go online.
Figure 2
Figure 2
Filament heights over time from a representative simulation run with d = 13 nm. The upper filament trajectories at the bundle tip are highlighted in blue, the partially collapsed filament trajectories are shown in red. All filaments are accounted for in these two categories during an identified metastable state. Three distinct metastable states are visible in order of appearance in the graph: (A) three completely collapsed filaments with the remainder at the tip of the bundle; (B) one of the inner filaments collapsed partway; and (C) two inner filaments collapsed partway. (Insets) Spatial configuration of the metastable states. (Dashed lines) Filament heights calculated from Eq. 6. (Shaded lines) Transient states between metastable configurations.
Figure 3
Figure 3
The spatial distribution of full-length filaments in the actin filament bundle inside the filopodium, displayed for the three most prevalent configurations (a) out of 3 found for d = 11 nm, (b) out of 7 found for d = 12 nm, and (c) out of 16 found for d = 13 nm. A solid circle indicates full-length filaments, and white space indicates partially or fully collapsed filaments. The numbers above the individual states indicate the percentage of total simulation time spent in that state. To see this figure in color, go online.
Figure 4
Figure 4
(a) Sketch of the one-dimensional diffusion channels considered as part of the mean-field model for a filopodium with two distinct filament heights. The two channels exhibit x-dependent piecewise linear concentrations c1, c2, c3, and c4. The lower channel changes its cross section at position L1 due to the presence of one or more filament tips. At position L2, both channels merge and the cross-sectional area changes again with A1 + A3 < A4. The membrane is at L = L2 + 25 nm. Polymerization of G-actin is implemented via sinks with strength k1 and k2 at positions L1 and L2, respectively. (b) Mean-field G-actin concentration profiles in the three channels for metastable configuration (C) displayed in Fig. 2 together with data from stochastic simulations. (c) Plot of the roots of the two stability conditions (Eq. 6) as a function of L1 and L2 for the same configuration. The points of filament stability where both conditions are true simultaneously are indicated by red dots. Light gray lines show the flow of the stability conditions. The hatched area indicates the unphysical regime L1 ≥ L2.
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References

    1. Mattila P.K., Lappalainen P. Filopodia: molecular architecture and cellular functions. Nat. Rev. Mol. Cell Biol. 2008;9:446–454. - PubMed
    1. Small J., Rottner K. Elementary cellular processes driven by actin assembly: lamellipodia and filopodia. In: Carlier M.-F., editor. Actin-based Motility. Springer; New York: 2010. pp. 3–33.
    1. Han Y.-H., Chung C.Y., Firtel R.A. Requirement of a vasodilator-stimulated phosphoprotein family member for cell adhesion, the formation of filopodia, and chemotaxis in Dictyostelium. J. Biol. Chem. 2002;277:49877–49887. - PubMed
    1. Dent E.W., Gertler F.B. Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron. 2003;40:209–227. - PubMed
    1. Maletic-Savatic M. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science. 1999;283:1923–1927. - PubMed

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