A guiding principle in self-assembly is that, for high production yield, nucleation of structures must be significantly slower than their growth. However, details of the mechanism that impedes nucleation are broadly considered irrelevant. Here, we analyze self-assembly into finite-sized target structures employing mathematical modeling. We investigate two key scenarios to delay nucleation: (i) by introducing a slow activation step for the assembling constituents and, (ii) by decreasing the dimerization rate. These scenarios have widely different characteristics. While the dimerization scenario exhibits robust behavior, the activation scenario is highly sensitive to demographic fluctuations. These demographic fluctuations ultimately disfavor growth compared to nucleation and can suppress yield completely. The occurrence of this stochastic yield catastrophe does not depend on model details but is generic as soon as number fluctuations between constituents are taken into account. On a broader perspective, our results reveal that stochasticity is an important limiting factor for self-assembly and that the specific implementation of the nucleation process plays a significant role in determining the yield.
arXiv:1905.09912v2 [physics.bio-ph] 18 Mar 2020 2 Model definitionWe model the assembly of a fixed number of well-defined target structures from limited resources. Specifically, we consider a set of S different species of constituents denoted by 1, . . . , S which assemble into rings of size L. The cases S = 1 and 1 < S ≤ L (S = L) are denoted as homogeneous and partially (fully) heterogeneous, respectively. The homogeneous model builds on previous work on virus capsid [3,17], linear protein filament assembly [7,27,28] and aggregation and polymerization models [24]. The heterogeneous model in turn links to previous model systems used to study, for example, DNA-brick-based assembly of heterogeneous structures [6,19,30]. We emphasize that, even though strikingly similar experimental realizations of our model exist [11,32,36], it is not intended to describe any particular system. The ring structure represents a general linear assembly process involving building