High-symmetry ill-fitting subunits in 3D form aggregates of all dimensions

TL;DR

This study theoretically explores how three-dimensional, ill-fitting deformable protein-like subunits self-assemble into various aggregate morphologies, revealing conditions that favor filament formation and providing insights into controlling protein aggregation.

Contribution

The paper introduces a theoretical model predicting diverse aggregate morphologies of ill-fitting subunits based on their mechanics and adhesion, extending understanding of 3D protein aggregation mechanisms.

Findings

Zero-dimensional clusters, bulks, filaments, and layers can form depending on parameters.

Poorly compressible, moderately adhesive subunits favor filament formation.

Mechanisms could be investigated in more realistic protein models.

Abstract

Proteins can combine into functional elements in living cells or self-assemble into unwanted structures in a number of diseases. The resulting aggregates often display filamentous morphologies across a large range of protein shapes and molecular interactions. This has led to the suggestion that filament formation could be a generic outcome of the aggregation of geometrically complex, ill-fitting objects, although such a mechanism has not been demonstrated in three dimensions. To address this problem, we theoretically study the self-assembly of three-dimensional identical, ill-fitting deformable subunits mimicking globular proteins in solution. In our model, self-assembling subunits incur deformations that accumulate as the aggregate size increases and can eventually hamper further assembly. We analytically predict the ground state morphologies of the resulting aggregates as a function of the subunit adhesivity and elasticity by mapping their mechanics onto those of two incompatible, interconnected networks. We find that zero-dimensional clusters, three-dimensional bulks as well as symmetry-broken one-dimensional filaments and two-dimensional layers can all form depending on assembly parameters. Poorly compressible, moderately adhesive subunits favor filaments. These findings hint at a generic pathway to control self-assembly in three dimensions and suggests that such mechanisms could be investigated in more realistic protein models.