Enzyme-responsive Microgels

动态的生物过程受到酶的催化活性的严格调控。指导或干预这些过程的能力为下一代医疗干预带来了希望。正是在这种背景下，我们的目标是开发新的微凝胶颗粒，将酶的生物催化作用转化为机械反应。我们之前的工作已经证明，原则上这是可能的，我们现在希望进一步探索这一领域，并解决四个挑战，这将使我们更接近生物医学应用。它们是：(i)建立酶反应微凝胶颗粒，其尺寸比我们之前报道的水凝胶珠小两个数量级，并且应该具有更快的响应时间；（ii）建立酶反应微凝胶分散体，以可逆的流体到凝胶转变的形式显示受控的机械反应；（iii）建立对酶（激酶/磷酸酶）组合有反应的完全可逆系统；（iv）首次证明了使用这些酶反应性微凝胶颗粒指导细胞反应的可能性。微凝胶是亚微米大小的聚合物胶体颗粒，在良好的溶剂中或粒子电荷增加时膨胀（膨胀）。我们将用肽致动器使这些微凝胶颗粒功能化，这些微凝胶颗粒被酶识别和切割，从而触发颗粒中电荷平衡的偏离。独特的是，这些酶反应微凝胶将在恒定pH和温度的水条件下局部工作，这在生物医学应用中提供了比现有刺激反应材料非常显著的优势。该合作项目将为两名博士生提供令人兴奋的，多学科的项目，在一流的研究环境。一个成功的结果将为按需给药和微创软组织修复的生物反应（纳米）技术开辟新的途径。

Dynamic biological processes are tightly regulated by the catalytic activity of enzymes. The ability to direct, or otherwise interfere with, these processes holds promise for next generation medical interventions. It is in this context that we aim to develop new microgel particles that convert biocatalytic action of enzymes into mechanical responses. Our previous work has demonstrated that this is possible, in principle, and we now wish to explore this area further and address four challenges that will bring us a step closer to biomedical applications. They are: (i) establishing enzyme-responsive microgel particles that are two orders in magnitude smaller in size compared to our previously reported hydrogel beads and should have much faster response times; (ii) establishing enzyme-responsive microgel dispersions that display controlled mechanical response in the form of reversible fluid-to-gel transitions; (iii) establishing fully reversible systems that respond to combinations of enzymes (kinase/phosphatase); (iv) demonstrating, for the first time, the possibility of directing cellular responses using these enzyme-responsive microgel particles. Microgels are sub-micrometer sized polymer colloid particles that expand (swell) in a good solvent or when the particle charge increases. We will functionalise these microgel particles with peptide actuators that are recognised and cleaved by enzymes, thereby triggering a departure from the charge balance in the particles Uniquely, these enzyme-responsive microgels will operate locally, under aqueous conditions at constant pH and temperature which provides very significant advantages over existing stimuli-responsive materials in the context of biomedical applications. This collaborative project will provide two PhD students with exciting, multi-disciplinary projects in top class research environments. A successful outcome will open up new avenues of bioresponsive (nano) technologies for on demand drug delivery and minimally-invasive soft tissue repair.