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快速转变到另一种状态。当反应被其产物催化时，这些由运动控制的细胞开关由反馈驱动，例如自动催化。反馈也是细菌和酵母等细胞系统活动同步的核心。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，开发了遗传电路来创建触发开关、化学振荡和大肠杆菌细胞中振荡的同步。通过计算研究和实验，我们将设计结合两个组件的仿生开关：反应动力学中的反馈和微粒子中反应的区隔。这项研究将为生物自组织提供洞察，并在分析或“智能”材料科学中具有潜在的应用。这项研究的第一部分涉及为化学反馈设计新的反应网络，为此，我们将使用自然的催化剂：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、有效性和生物相容性，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势，例如在存在噪声的情况下对化学信号的快速、稳健的反应。为了创造细胞开关，反应的酶催化剂将被固定在微粒中。当浸泡在反应物的浴缸中时，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保持系统远离平衡。通过对动力学的操纵，可以实现微粒子的化学开关、滞后、化学脉冲、图案或自运动等令人兴奋的特征。一组组酶微粒通过将化学物质释放到周围的溶液中相互作用，从而为研究生物启发的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.