Modelling the Self-Assembly of Elastomeric Proteins Provides Insights into the Evolution of Their Domain Architectures

Abstract

Elastomeric proteins have evolved independently multiple times through evolution. Produced as monomers, they self-assemble into polymeric structures that impart properties of stretch and recoil. They are composed of an alternating domain architecture of elastomeric domains interspersed with cross-linking elements. While the former provide the elasticity as well as help drive the assembly process, the latter serve to stabilise the polymer. Changes in the number and arrangement of the elastomeric and cross-linking regions have been shown to significantly impact their assembly and mechanical properties. However, to date, such studies are relatively limited. Here we present a theoretical study that examines the impact of domain architecture on polymer assembly and integrity. At the core of this study is a novel simulation environment that uses a model of diffusion limited aggregation to simulate the self-assembly of rod-like particles with alternating domain architectures. Applying the model to different domain architectures, we generate a variety of aggregates which are subsequently analysed by graph-theoretic metrics to predict their structural integrity. Our results show that the relative length and number of elastomeric and cross-linking domains can significantly impact the morphology and structural integrity of the resultant polymeric structure. For example, the most highly connected polymers were those constructed from asymmetric rods consisting of relatively large cross-linking elements interspersed with smaller elastomeric domains. In addition to providing insights into the evolution of elastomeric proteins, simulations such as those presented here may prove valuable for the tuneable design of new molecules that may be exploited as useful biomaterials.

Author Summary

Elastomeric proteins such as elastin, resilin, abductin and wheat gluten represent a remarkable class of self-assembling proteins that provide properties of extensibility and elastic recoil. Although unrelated from an evolutionary viewpoint, these proteins nonetheless share a common sequence design involving highly repetitive elastomeric regions interspersed with elements capable of forming cross-links that help stabilize the formation of polymers. Attempts to explore the influence of domain architecture on the self-assembly and mechanical properties of elastomeric proteins at the molecular level have largely been hindered by a general lack of detailed structural information. Here we introduce a novel theoretical study based on random walks to simulate the self-assembly of elastomeric proteins. Applying this model, we explored the impact of different configurations of elastomeric and cross-linking elements on the stability of the resultant polymer. Through exploring the complex relationships between elastomeric domains, required to drive self-assembly, and cross-linking domains, required for structural integrity, results from these simulations provide insights into the molecular basis for the evolution of elastomeric proteins as well as help guide the rational design of novel elastomeric-peptides.