Elastin is the dominant building block of elastic fibers that impart structural integrity and elasticity to a range of important tissues, including the lungs, blood vessels, and skin. The elastic fiber assembly process begins with a coacervation stage where tropoelastin monomers reversibly self-assemble into coacervate aggregates that consist of multiple molecules. In this paper, an atomistically based coarse-grained model of tropoelastin assembly is developed. Using the previously determined atomistic structure of tropoelastin, the precursor molecule to elastic fibers, as the basis for coarse-graining, the atomistic model is mapped to a MARTINI-based coarse-grained framework to account for chemical details of protein–protein interactions, coupled to an elastic network model to stabilize the structure. We find that self-assembly of monomers generates up to ∼70 ​nm of dense aggregates that are distinct at different temperatures, displaying high temperature sensitivity. Resulting assembled structures exhibit a combination of fibrillar and globular substructures within the bulk aggregates. The results suggest that the coalescence of tropoelastin assemblies into higher order structures may be reinforced in the initial stages of coacervation by directed assembly, supporting the experimentally observed presence of heterogeneous cross-linking. Self-assembly of tropoelastin is driven by interactions of specific hydrophobic domains and the reordering of water molecules in the system. Domain pair orientation analysis throughout the self-assembly process at different temperatures suggests coacervation is a driving force to orient domains for heterogeneous downstream cross-linking. The model provides a framework to characterize macromolecular self-assembly for elastin, and the formulation could easily be adapted to similar assembly systems.

弹性蛋白是弹性纤维的主要组成部分，可赋予一系列重要组织包括肺，血管和皮肤以结构完整性和弹性。弹性纤维组装过程从凝聚阶段开始，在该阶段，原弹性蛋白单体可逆地自组装为凝聚分子，该凝聚体由多个分子组成。本文建立了一个基于原子的原弹性蛋白组装的粗粒度模型。使用先前确定的弹性蛋白的前体分子原弹性蛋白的原子结构作为粗粒度的基础，将原子模型映射到基于MARTINI的粗粒度框架，以解释蛋白质间相互作用的化学细节弹性网络模型来稳定结构。我们发现单体的自组装产生了高达70纳米的致密聚集体，这些聚集体在不同温度下是不同的，显示出高温敏感性。所得的组装结构在散装骨料中表现出原纤维状和球形亚结构的组合。结果表明，在凝聚的最初阶段，通过定向组装可以增强原弹性蛋白组装体向高级结构的聚结，从而支持了实验观察到的异质交联的存在。原弹性蛋白的自组装由特定疏水域的相互作用和系统中水分子的重排驱动。在不同温度下整个自组装过程中的畴对取向分析表明，凝聚是使畴取向以进行异质下游交联的驱动力。该模型提供了表征弹性蛋白大分子自组装的框架，并且该制剂可以轻松地适应类似的组装系统。