CAREER:Self-Healing Under Flow: From Single Molecule Dynamics to Regenerative Scaffold Formation

该职业奖支持流动下自我修复的理论和计算研究和教育，灵感来自于无处不在但远未被理解的血液凝固过程。当血液凝结时，一个生物聚合物细胞网络会在化学和机械刺激下形成，堵塞渗漏并愈合伤口。这些流动网络的形成构成了生物聚合物科学的新范式，并且有可能揭示这些生物材料的新特性，因为它们是在强非平衡条件下形成的。这里提出的工作将利用理论和模拟从微观的角度来揭示这些聚合物-细胞复合材料的整体形成过程，以获得复杂流动中自组装、粘附和自修复过程的基本知识，不仅提供关于凝块如何产生和控制的知识，而且为未来研究解决流动中自组装问题提供指导。最终，我们相信通过利用流动诱导的相互作用和分子构象变化，一套新的材料原理可以在广泛的领域应用，包括药物输送，涂层和密封剂，自我再生材料和粘合剂。该项目还旨在激励年轻人从事科学事业，成为下一代杰出的研究人员。教育和推广活动将包括对来自当地社区大学的少数民族学生的夏季辅导，开发使用网络基础设施的综合课程，以及创建一个计算套件，使所有年龄的学生都能与软材料进行互动和实验。这个职业奖支持理论和计算研究，以及受血凝块启发的自我修复的教育。血块是血液中许多血小板在受伤部位聚集并粘在一起形成的。然而，在强流动条件下，血小板不能粘在一起，因此不能形成凝块。为了减轻这一缺陷，大自然开发了冯氏血友病因子，这是一种长响应的生物聚合物，它是一个具有重复原子块的大分子。血管性血友病因子揭开并暴露了一堆粘着的部位，它通过这些粘着的部位连接血小板，并将血小板粘在损伤部位。这种生物聚合物-血小板复合物被称为栓子，它是我们身体对受伤血管的第一反应。然而，这种塞子形成的过程仍远未被理解。本项目旨在通过理论和模拟来阐明凝块形成的机制。它将对桥塞形成过程中发生的重要过程进行微观观察。这项研究为在各种技术相关领域创造新材料提供了理论指导，如药物输送、涂料和密封剂、自再生材料和粘合剂。该项目还旨在激励年轻人从事科学事业，成为下一代杰出的研究人员。教育和推广活动将包括对来自当地社区大学的少数族裔学生的暑期辅导，开发利用网络基础设施的综合课程，以及创建一个计算套件，让所有年龄段的学生都能与塑料等软材料进行互动和实验。

Technical SummaryThis CAREER award supports theoretical and computational research and education on self-healing under flow, inspired by the ubiquitous, yet far from understood, process of blood clotting. When blood clots, a biopolymer-cellular network that plugs the leak and heals the wound is developed in response to chemical and mechanical stimuli. The formation of these networks in flow constitutes a new paradigm in biopolymer science, and has the potential to uncover new properties of these biomaterials since they are formed under strong non-equilibrium conditions. The work here proposed will utilize theory and simulations to unravel the overall formation process of these polymer-cell composites from a microscopic point of view to gain fundamental knowledge of the process of self-assembly, adhesion, and self-healing in complex flows, providing not only knowledge on how clots are initiated and controlled, but a guideline for future studies that address the problem of self-assembly in flow. Ultimately, we believe that by exploiting flow-induced interactions and molecular conformational changes, a new set of materials principles can emerge with applications in a wide variety of fields including drug-delivery, coatings and sealing agents, self-regenerative materials, and adhesives. This project also aims to inspire younger people to pursue a career in science and be the next generation of outstanding researchers. Education and outreach activities will include summer mentoring of minority students from local community colleges, the development of integrated courses that employ cyberinfrastructure, and the creation of a computational suite that will allow students from all ages to interact and experiment with soft-materials.Non-technical Summary This CAREER award supports theoretical and computational research and education on self-healing under flow inspired by how blood clots. A clot is formed in blood by accumulating and sticking together many platelets at the site of injury. In strong flowing conditions, however, platelets cannot stick to themselves and thus no clot can be formed. To alleviate this deficiency nature has developed the von Willebrand factor, a long responsive biopolymer which is a large molecule with repeating blocks of atoms. The von Willebrand factor unravels and exposes a bunch of sticky sites with which it interconnects platelets, as well as stick them to the injury site. The biopolymer-platelet composite is called the plug and it is our body's first response to an injured vessel. However, the process by which this plug forms is still far from understood. This project aims to elucidate the mechanism by which clots form using theory and simulations. It will develop a microscopic view of the important processes occurring during plug formation. This research contributes theoretical guidance for creating novel materials in a wide variety of technologically relevant fields such as drug-delivery, coatings and sealing agents, self-regenerative materials, and adhesives. This project also aims to inspire younger people to pursue a career in science and be the next generation of outstanding researchers. Education and outreach activities will include summer mentoring of minority students from local community colleges, the development of integrated courses that employ cyberinfrastructure, and the creation of a computational suite that will allow students from all ages to interact and experiment with soft-materials like plastics.