Kinetic Switches: Exploiting Feedback in Enzyme Microparticles

许多生物过程需要在超临界刺激下从一种化学状态迅速过渡到另一种化学状态。这些动力学控制的细胞开关由反馈驱动，如自催化，当反应被其产物催化时。在细菌和酵母等细胞系统中，反馈也是活动同步的核心。人们对产生反馈驱动行为的反应网络的设计非常感兴趣，例如，在大肠杆菌细胞中开发了用于创建拨动开关、化学振荡和振荡同步的遗传电路。通过计算研究和实验，我们将设计结合两个组成部分的仿生开关：反应动力学的反馈和微粒反应的区隔化。这项研究将提供对生物自组织的深入了解，并在分析或“智能”材料科学中具有潜在的应用。这项研究的第一个组成部分涉及设计新的化学反馈反应网络，为此我们将使用大自然的催化剂：酶。酶为传感器、药物输送装置和生物反应器等广泛应用提供了特异性、效率和生物相容性，但与自催化相关的丰富行为尚未得到开发。我们将研究可能的优点，例如在存在噪声的情况下对化学信号的快速，稳健的响应。为了制造细胞开关，反应的酶催化剂将被固定在微粒中。当浸入反应物中时，微粒从周围的溶液中获得化学“燃料”，以类似于细胞的方式自然地使系统远离平衡状态。通过对动力学的操纵，诸如化学开关、滞后、化学脉冲、模式或微粒的自运动等令人兴奋的特征是可能的。酶微粒群通过向周围溶液中释放化学物质而相互作用，从而为研究生物启发细胞系统中的集体行为和自组织创造了新的机会。

Many biological processes require a rapid transition from one chemical state to another following a supercritical stimulus. These kinetically-controlled cell switches are driven by feedback such as autocatalysis, when a reaction is catalysed by its product. Feedback also lies at the heart of synchronisation of activity in cellular systems such as bacteria and yeast. There has been great interest in the design of reaction networks that produce feedback-driven behaviour, for example, genetic circuits were developed to create a toggle switch, chemical oscillations and synchronisation of oscillations in E. coli cells. Through computational studies and experiments, we will design bio-inspired switches combining two components: feedback in the reaction kinetics and compartmentalisation of the reaction in microparticles. This research will provide insight into biological self-organisation as well as having potential applications in analytical or "smart" materials science. The first component of the research involves designing novel reaction networks for chemical feedback and for this we will use nature's catalysts: enzymes. Enzymes offer specificity, efficiency and biocompatibility for widespread applications such as sensors, drug delivery devices and bio-reactors but the wealth of behaviour associated with autocatalysis has yet to be exploited. We will investigate possible advantages such as such as a fast, robust response to a chemical signal in the presence of noise. In order to create a cellular switch, the enzyme catalyst for the reaction will be immobilised in microparticles. When immersed in a bath of reactants, the microparticles obtain chemical "fuel" from the surrounding solution, naturally maintaining the system far-from-equilibrium in a similar manner to cells. By manipulation of the kinetics, exciting features such as a chemical switch, hysteresis, chemical pulses, patterns or self-motion of the microparticles are possible. Groups of enzyme microparticles interact with each other via the release of chemicals into the surrounding solution, thus creating a new opportunity for the examination of collective behaviours and self-organisation in bio-inspired cellular systems.