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Assembly Factors Resolve Speed and Encoding Bottlenecks in Multifarious Self-Assembly

Félix Benoist and Pablo Sartori*

  • *Contact author: pablo.sartori@gimm.pt
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PRX Life 4, 033021 – Published 27 August, 2026

DOI: https://doi.org/10.1103/5w6h-l93l

Abstract

Cytoplasm is a heterogeneous mixture containing many types of proteins that self-assemble into a wide variety of complexes. The accuracy and speed of cytoplasmic self-assembly is astonishing because it involves the correct identification of components shared among different structures, despite pervasive thermal fluctuations. Typical toy models of self-assembly are based on the specificity of binding energies among components. However, kinetics plays a key role in biological self-assembly, often catalyzed by a plethora of assembly factors. Building on this observation, we extend a previous heteropolymer growth model to describe the retrieval of two-dimensional structures via quasi-two-dimensional growth. We find that the self-assembly of structures in this model is subject to strong speed and encoding bottlenecks. Moreover, we show that these bottlenecks can be suppressed by increasing the connectivity of a small fraction of components. This mechanism of kinetically controlling a small number of critical binding events provides a simple explanation for the timely assembly of large heteromeric protein complexes and suggests a unifying principle for the role of assembly factors.

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PRX Life 4, 033021– Published 27 August, 2026
  • Received 7 January 2026
  • Accepted 15 July 2026
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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.

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