NSF2026: EAGER: Harnessing Protein Disorder in the Design of Ordered Cellular Materials

非技术概述在NSF材料研究部生物材料计划和综合活动办公室NSF 2026基金计划的支持下，特拉华大学的Das和Kiik教授因其“在有序细胞材料设计中利用蛋白质无序”的建议而获奖。这项研究涉及这样一个事实，即合成生物材料必须包括“智能”功能特性--自我调节、自我修复、环境响应和自我可持续--才能作为工程生物材料(ELM)发挥作用，这些材料有望给当今的材料技术带来革命性的变化。榆树可以提供对生命器官的发育、多器官系统的组织以及自主感知和治疗材料的生产的洞察。然而，由于缺乏对材料的组织和细胞和分子在多个长度尺度上的放置的控制，工程生物材料的大规模生产一直难以实现。这项建议通过开发微结构亲水聚合物水凝胶来解决这一差距。这项提议中使用的聚合物溶液具有在特定化合物存在的情况下可逆改变浓度的独特能力，这将允许使用微米级机器人来输送这些化合物来生产图案化水凝胶。这些方法将与细胞整合，产生高度有序的细胞凝胶材料，具有高细胞活力。对水凝胶性质的精确和可编程的空间控制将使干细胞的局部分化成为工程生物材料，并随后制造复杂的组织，以促进国民健康。该项目包括一项让K-12女孩和她们的照顾者参与动手机器人活动的计划，这些活动将加强学习策略，并激发人们对科学和工程的兴趣。研究生和本科生将在融合材料科学和机器人的跨学科环境中接受培训。技术概述拟议的研究将开发一种新的方法，以制造具有功能特性的可寻址的、微机器人控制的生物工程材料(ELM)。ELMS的大规模制造需要可靠地控制材料的组织和细胞和分子在多个长度尺度上的放置。这一提议的总体目标是主要基于生物弹性体resilin衍生的类resilin多肽(RLP)，生成具有不同机械性能的规则微结构区域的聚合物水凝胶。基于RLP的溶液在小分子和聚合物共溶体存在的情况下具有可逆改变浓度的独特能力。这一建议中的工作假设是，聚乙二醇微机器人的输送将迅速引发微型机器人附近局部RLP浓度的增加，导致在生物弹性体中形成机械上不同的微结构区域。同时使用数字微镜显示(DMD)系统将允许光的共局部化，从而引发交联并以前所未有的精度产生局域化微结构。磁性微型机器人控制策略的发展将使微型机器人群的控制成为可能，以实现大规模的聚乙二醇输送。能够高精度地触发以所需坐标传递分子的微型机器人还将能够对生物活性分子和可用于暂时改变细胞功能的因子进行时空控制。为了确认细胞在这些微生物图案化、细胞相容的生物弹性水凝胶中/上的存活、代谢活性和增殖能力，商业上可获得的人间充质干细胞(HMSCs)将被包裹在/在图案化的RLP水凝胶中，并将对其增殖进行测试。建议的研究是针对NSF2026 IDEA机器获奖作品“工程生物材料”提交的。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Non-technical summaryWith support from the Biomaterials Program of the NSF Division of Materials Research, and the NSF 2026 Fund Program in the Office of Integrated Activities, Professors Das and Kiik at University of Delaware are awarded for their proposal "Harnessing Protein Disorder in the Design of Ordered Cellular Materials". The research involves the fact that synthetic biological materials must include “smart” functional properties – self-regulation, self-healing, environmental responsiveness, and self-sustainability – to function as engineered living materials (ELMs), which are poised to revolutionize present-day materials technologies. ELMs can offer insights into the development of living organs, the organization of multiple organ systems, and the production of autonomously sensing and healing materials. However, the large-scale manufacture of engineered living materials has been difficult to achieve, owing to a lack of control of both materials’ organization and cell and molecule placement over multiple length scales. This proposal addresses this gap by developing microstructured hydrophilic polymer hydrogels. The polymer solutions used in this proposal have the unique capability of reversibly changing concentration in the presence of specific compounds, which will allow the use of micron-scale robots to deliver these compounds to produce patterned hydrogels. These approaches will be integrated with cells to generate highly ordered cell-gel materials with high cell viability. The precise and programmable spatial control of hydrogel properties will enable localized differentiation of stem cells to form engineered living materials, and subsequent manufacture of complex tissues for advancing national health. The project includes a plan to engage K-12 girls and their caregivers in hands-on robotics activities that will enhance learning strategies and stimulate interest in science and engineering. Graduate and undergraduate students will receive training in an interdisciplinary environment blending materials science and robotics.Technical summaryThe proposed research will develop a new approach for making addressable, microrobotically-controlled engineered living materials (ELMs) with functional properties. The large-scale manufacture of ELMs requires the reliable control of both materials’ organization and cell and molecule placement over multiple length scales. The overarching goal of this proposal is to generate polymer hydrogels with regular microstructured regions of distinct mechanical properties, based largely on resilin-like polypeptides (RLPs) derived from the bioelastomer resilin. RLP-based solutions have the unique capability of reversibly changing concentration in the presence of small-molecule and polymeric co-solutes. The working hypothesis in this proposal is that the microrobotic delivery of polyethylene glycol (PEG) will rapidly trigger a locally increased concentration of RLPs near microrobots, leading to the formation of mechanically distinct microstructured regions in the bioelastomer. The coincident use of a digital micromirror display (DMD) system will permit the co-localization of light, thus initiating crosslinking and generating localized microstructures with unprecedented precision. The development of magnetic microrobot control strategies will enable control of microrobotic swarms for large-scale delivery of PEG. Microrobots capable of triggered delivery of molecules at desired coordinates with high precision will also enable spatiotemporal control of bioactive molecules and factors which can be used to temporally alter cellular function. To confirm the survival, metabolic activity, and proliferative capacity of cells in/on these microrobotically patterned, cytocompatible bioelastomeric hydrogels, commercially available human mesenchymal stem cells (hMSCs) will be encapsulated in/on the patterned RLP-based hydrogels and their proliferation will be tested.The proposed research was submitted in response to the NSF2026 Idea Machine winning entry "Engineered Living Materials".This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.