Abstract:
Artificial biomolecular condensates are emerging as a versatile approach to organize molecular targets and reactions without the need for lipid membranes. Here we ask whether the temporal response of artificial condensates can be controlled via designed chemical reactions. We address this general question by considering a model problem in which a phase separating component participates in reactions that dynamically activate or deactivate its ability to self-attract. Through a theoretical model we illustrate the transient and equilibrium effects of reactions, linking condensate response and reaction parameters. We experimentally realize our model problem using star-shaped DNA motifs known as nanostars to generate condensates, and we take advantage of strand invasion and displacement reactions to kinetically control the capacity of nanostars to interact. We demonstrate reversible dissolution and growth of DNA condensates in the presence of specific DNA inputs, and we characterize the role of toehold domains, nanostar size, and nanostar valency. Our results will support the development of artificial biomolecular condensates that can adapt to environmental changes with prescribed temporal dynamics.
摘要:
人工生物分子缩合物正在成为一种在不需要脂质膜的情况下组织分子靶标和反应的通用方法。在这里,我们询问是否可以通过设计的化学反应来控制人工冷凝物的时间响应。我们通过考虑一个模型问题来解决这个普遍问题,在该模型中,相分离成分参与了动态激活或停用其自吸引能力的反应。通过理论模型,我们说明了反应的瞬态和平衡效应,连接缩合反应和反应参数。我们通过实验实现了我们的模型问题,使用被称为纳米星的星形DNA基序来产生凝聚物,我们利用链侵入和置换反应来动力学控制纳米星相互作用的能力。我们证明了在存在特定DNA输入的情况下,DNA缩合物的可逆溶解和生长,我们描述了立足点域的作用,纳米星尺寸,和纳米星价。我们的结果将支持人造生物分子缩合物的开发,该缩合物可以以规定的时间动力学适应环境变化。