Molecular Assembly Lines in Active Droplets

Open Access

Molecular Assembly Lines in Active Droplets

Tyler S. Harmon and Frank Jülicher

Phys. Rev. Lett. 128, 108102 – Published 9 March 2022

Abstract

Large protein complexes are assembled from protein subunits to form a specific structure. In our theoretic work, we propose that assembly into the correct structure could be reliably achieved through an assembly line with a specific sequence of assembly steps. Using droplet interfaces to position compartment boundaries, we show that an assembly line can be self-organized by active droplets. As a consequence, assembly steps can be arranged spatially so that a specific order of assembly is achieved and incorrect assembly is strongly suppressed.

Received 24 June 2020
Revised 30 November 2021
Accepted 21 January 2022

DOI:https://doi.org/10.1103/PhysRevLett.128.108102

Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. Open access publication funded by the Max Planck Society.

Published by the American Physical Society

Physics Subject Headings (PhySH)

Biological self-organization Biomolecular interactions Biomolecular self-assembly Biomolecular structure Cell assembly Chemical kinetics, dynamics & catalysis Diffusion

Cellular compartments Proteins RNA

Finite-element method

Physics of Living SystemsNonlinear DynamicsInterdisciplinary Physics

Authors & Affiliations

Tyler S. Harmon ^1,2,3,* and Frank Jülicher ^1,4,5,†

¹Max Planck Institute for the Physics of Complex Systems, Nöthnitzerstraße 38, 01187 Dresden, Germany
²Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany
³Leibniz-Institut für Polymerforschung Dresden e.V., Hohestraße 6, 01069 Dresden, Germany
⁴Center for Systems Biology Dresden, 01307 Dresden, Germany
⁵Cluster of Excellence Physics of Life, TU Dresden, 01062 Dresden, Germany

^*tylerharmon@pks.mpg.de
^†julicher@pks.mpg.de

Article Text

Click to Expand

Supplemental Material

Click to Expand

References

Click to Expand

Issue

Vol. 128, Iss. 10 — 11 March 2022

Reuse & Permissions

Author publication services for translation and copyediting assistance advertisement

Images

Figure 1
Spatial organization of macromolecular assembly. (a) 1D arrangement of compartments for molecular assembly. Component $C_{1}$ is produced in the left volume (green) and component $C_{2}$ is produced in the right volume (blue). Assembly of the complex $C_{12}$ occurs in the stage volume (orange). Assembly can be localized to a band between the left and right volumes (dashed line). The complex is exported via the right volume. (b) 3D arrangement of compartments for molecular assembly. Component $C_{1}$ is produced in the inner volume (green) and component $C_{2}$ is produced in the outer volume (blue). Assembly of the complex $C_{12}$ occurs in the stage volume (orange). Assembly can be localized to a spherical band between the inner and outer volumes (dashed line). The complex is exported via the outer volume.
Reuse & Permissions
Figure 2
Positioning of assembly steps in narrow regions. (a) Normalized assembly flux $Φ$ as a function of normalized position $x$ in the stage region for different values of the normalized influx $α$ of component $C_{2}$ [ $α = 70$ (blue), 50 (orange), 30 (green), 10 (yellow)]. (b) Steady state concentrations of components $C_{1}$ (dashed) and $C_{2}$ (solid) for the same values of $α$ as in (a). Shown are numerical solutions of the minimal model given by Eqs. (2) and (3). (c) Cartoon schematic of how an assembly line could be organized. The foundation molecule tends to diffuse to the right progressing through the different association bands. Progressing to each sequential association bands adds another available brick that can bind to the foundation. Parameter values are $J = 0.31$ , $D = 0.039$ , $k = 5.9$ , $β = 10$ , and $L = 1$ .
Reuse & Permissions
Figure 3
Self-organized molecular assembly lines. (a) Scheme of the on pathway assembly steps (blue, red, green, and yellow arrows) and off-pathway dead ends (pink arrows). Here, $F_{0}$ represents the foundation and $B_{1}$ , $B_{2}$ , $B_{3}$ , $B_{4}$ represent the bricks. The on-pathway intermediates are denoted $F_{1}$ , $F_{2}$ , $F_{3}$ , and $F_{4}$ is the correctly assembled product. (b) Fraction of completed (green), incomplete (yellow), and incorrect (red) assemblies that leave the stage in steady state as a function of the association rate $k$ . (c) Radial profiles of total assembly fluxes $Φ = 4 π r^{2} k n_{F, i} n_{B, j}$ at steady state for the four on-pathway associations (blue, red, green, yellow) and the off-pathway associations (pink) for association rate $k = 0.038 {nM}^{- 1} s^{- 1}$ . Here, $n_{F, i}$ and $n_{B, j}$ are concentrations of associating components. (d) same as (c) but for $k = 0.27 {nM}^{- 1} s^{- 1}$ . The curves shown in (c) and (d) correspond to the assembly steps shown in (a) in the same color. Shown in (b)–(d) are numerical solutions for spherical geometry and parameter values $J = 10 {μ m}^{3} {nM s}^{- 1}$ , $β_{F} = 1.26 {μ m}^{3} s^{- 1}$ , $β_{B} = 1.26 {μ m}^{3} s^{- 1}$ , $r_{1} = 0.25 μ m$ , $r_{2} = 1.0 μ m$ , $D_{F} = 0.01 {μ m}^{2} s^{- 1}$ , $D_{B, i} = 0.01 {μ m}^{2} s^{- 1}$ , and $α_{B, i} = (138, 82, 50, 29) {μ m}^{3} {nM s}^{- 1}$ for $i = (1, 2, 3, 4)$ .
Reuse & Permissions

Physical Review Letters