Department of Cancer Biology, Dana-Farber Cancer Institute , Boston, Massachusetts 02215, United States.
Nano Lett. 2017 Dec 13;17(12):7940-7944. doi: 10.1021/acs.nanolett.7b04336. Epub 2017 Nov 2.
Chemical clocks usually achieve well-defined temporal delays through concentration thresholding coupled to the production, degradation, activation, or inhibition of downstream effectors. In this way, the stochastic dynamics of many individual molecules yield essentially deterministic bulk behavior through ensemble averaging. As a result, their temporal evolution is governed by ensemble dynamics rather than by the behavior of an individual molecule or complex. Here, we present a general approach for the design of single-molecule clocks that permits quasi-deterministic control over the lifetime of single molecular interactions without any external synchronization. By coupling the dissociation of a bimolecular complex to a series of irreversible chemical steps, we interpose a well-defined time delay between binding and dissociation. The number and speed of irreversible steps can be varied to systematically tune both the lifetimes of complexes and the precision of the time delay, raising the prospect of localized timekeeping in nanoscale systems and devices.
化学时钟通常通过浓度门控与下游效应物的产生、降解、激活或抑制相结合来实现明确的时间延迟。通过这种方式，许多单个分子的随机动力学通过总体平均产生基本上确定的整体行为。因此，它们的时间演化受总体动力学而不是单个分子或复合物的行为控制。在这里，我们提出了一种设计单分子时钟的通用方法，该方法允许在没有任何外部同步的情况下对单个分子相互作用的寿命进行准确定性控制。通过将双分子复合物的解离与一系列不可逆化学步骤耦合，我们在结合和解离之间引入了明确的时间延迟。不可逆步骤的数量和速度可以变化，以系统地调整复合物的寿命和时间延迟的精度，从而为纳米级系统和设备中的局部计时带来了前景。
