Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.
Phys Rev Lett. 2021 Jun 25;126(25):258101. doi: 10.1103/PhysRevLett.126.258101.
Biomolecular condensates self-assemble when proteins and nucleic acids spontaneously demix to form droplets within the crowded intracellular milieu. This simple mechanism underlies the formation of a wide variety of membraneless compartments in living cells. To understand how multiple condensates with distinct compositions can self-assemble in such a heterogeneous system, which may not be at thermodynamic equilibrium, we study a minimal model in which we can "program" the pairwise interactions among hundreds of species. We show that the number of distinct condensates that can be reliably assembled grows superlinearly with the number of species in the mixture when the condensates share components. Furthermore, we show that we can predict the maximum number of distinct condensates in a mixture without knowing the details of the pairwise interactions. Simulations of condensate growth confirm these predictions and suggest that the physical rules governing the achievable complexity of condensate-mediated spatial organization are broadly applicable to biomolecular mixtures.
生物分子凝聚体在蛋白质和核酸自发分离形成液滴时自组装，这些液滴在拥挤的细胞内环境中形成。这种简单的机制是活细胞中各种无膜隔间形成的基础。为了了解在可能不是热力学平衡的这种异质体系中，具有不同成分的多个凝聚体如何能够自组装，我们研究了一个最小模型，在该模型中我们可以“编程”数百种物质之间的成对相互作用。我们表明，当凝聚体共享成分时，能够可靠组装的不同凝聚体的数量与混合物中的物质数量呈超线性增长。此外，我们表明，我们可以在不知道成对相互作用细节的情况下预测混合物中不同凝聚体的最大数量。凝聚体生长的模拟证实了这些预测，并表明控制凝聚体介导的空间组织可实现复杂性的物理规则广泛适用于生物分子混合物。
