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

技术概述这个职业奖项支持在血流作用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结过程。当血液凝结时，一种生物聚合物-细胞网络会对化学和机械刺激做出反应，从而堵塞泄漏并愈合伤口。这些流动网络的形成构成了生物聚合物科学的新范式，并有可能揭示这些生物材料的新性质，因为它们是在强烈的非平衡条件下形成的。本文提出的工作将利用理论和模拟从微观角度解开这些聚合物-细胞复合材料的整个形成过程，以获得复杂流动中自组装、粘合和自我修复过程的基础知识，不仅提供关于凝块如何引发和控制的知识，而且为未来解决流动中自组装问题的研究提供指导。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出现在广泛的领域，包括药物输送、涂层和密封剂、自再生材料和粘合剂。该项目还旨在激励年轻人追求科学事业，成为下一代杰出的研究人员。教育和外展活动将包括对当地社区大学的少数族裔学生的暑期指导，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，允许所有年龄段的学生与软材料互动和实验。非技术总结这个职业奖项支持理论和计算研究，以及在血液凝块启发下的自我修复教育。血液中的血栓是通过在损伤部位聚集和粘连许多血小板而形成的。然而，在强烈的流动条件下，血小板不能粘住自己，因此不会形成凝块。为了缓解这一缺陷，自然界开发出了von Willebrand因子，这是一种长响应的生物聚合物，是一种具有重复原子块的大分子。Von Willebrand因子解体并暴露出一堆粘性部位，它们与血小板相互连接，并将它们粘在损伤部位。这种生物聚合物-血小板复合材料被称为塞子，它是我们身体对受损血管的第一反应。然而，这个塞子形成的过程仍然远未被理解。本项目旨在通过理论和模拟来阐明血栓形成的机制。它将对堵塞物形成过程中发生的重要过程进行微观观察。这项研究为在药物输送、涂层和密封剂、自再生材料和粘合剂等广泛的技术相关领域创造新材料提供了理论指导。该项目还旨在激励年轻人追求科学事业，成为下一代杰出的研究人员。教育和外展活动将包括对当地社区大学的少数族裔学生进行暑期辅导，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，允许所有年龄段的学生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.