Enzyme-responsive Microgels

动态的生物过程受到酶的催化活性的严格调控。指导或以其他方式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。我们以前的工作表明，原则上这是可能的，现在我们希望进一步探索这一领域，解决四个挑战，使我们离生物医学应用更近一步。它们是：(I)建立与我们以前报道的水凝胶珠相比尺寸小两个数量级的酶反应微凝胶颗粒；(Ii)建立酶反应微凝胶分散体，以可逆液-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)组合做出反应的完全可逆系统；(Iv)首次展示使用这些酶反应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，在良好的溶剂中或当颗粒电荷增加时会膨胀(膨胀)。我们将用酶识别和切割的多肽致动器来功能化这些微凝胶颗粒，从而引发颗粒中电荷平衡的偏离。这些酶响应微凝胶将在水溶液条件下在恒定的pH和温度下局部工作，这在生物医学应用方面提供了比现有刺激响应材料非常显著的优势。这个合作项目将在顶级研究环境中为两名博士生提供令人兴奋的、多学科的项目。一个成功的结果将为按需给药和微创软组织修复开辟生物响应(纳米)技术的新途径。

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.