DMREF/Collaborative Research: Computationally Driven Design of Synthetic Tissue-Like Multifunctional Materials

在自然界中，活细胞结合形成能够集体行为的组织，例如感知和响应外部线索，交流，分类和储存化学物质，以及调整其机械特性以维持必要的负荷。生物组织实现这些理想的性能，因为仔细控制的内容，安排，和个别细胞的互连，一种方法，产生具有高水平的适应性，响应性和可调的机械强度的分层材料。在合成材料中复制这些类型的新兴特性仍然是一个重大的工程挑战。这个设计材料革命和工程我们的未来（DMREF）奖支持模仿活组织的组成，组织和特性的材料系统的基础研究和科学开发。具有精确组成和空间布置的类组织材料的计算主导设计寻求为人工组织替换、伤口愈合、软机器人和嵌入式计算技术中的应用提供可推广的解决方案。此外，该项目还将通过各种推广和研究活动，促进高中生、本科生和研究生，特别是第一代和代表性不足的群体的参与，支持STEM劳动力的技术和专业发展。该项目旨在研究由独立的细胞样隔室组成的合成组织，这些隔室通过机械拴系（即，作为合成细胞骨架的自组装嵌段共聚物微凝胶（BCP））和选择性转运（即，富含蛋白质的仿生膜（BM）作为选择性屏障）机制和结合刺激响应性（例如，通过聚合物和膜蛋白）进入隔室。计算方法结合联合收割机分子运输，刺激响应耦合变形的BCP，间室粘附，和生物膜力学来预测故障行为，紧急属性，和功能的组织样组件。理论，计算，BCP合成，3D生物打印和微尺度机械表征之间的迭代反馈循环是验证预测，通知模型开发和创建模块化数据库的项目的核心。通过了解BCP的可调疏水性和亲水性区域如何：1）在纳米尺度上与两亲性BM相互作用; 2）在微米尺度上自组装和缠结形成固体状凝胶; 3）在宏观尺度上在隔室之间交联以使整个组件刚性化。最终，该项目将提供定量知识库和模块化设计标准，以加速组装和使用多功能、刺激敏感、适应性强、坚韧且在平衡之外运行的分隔组织状材料。机械和制造创新在工程局和材料研究部在数学和物理局科学。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

In nature, living cells join to form tissues capable of collective behaviors, such as sensing and responding to external cues, communicating, sorting and storing chemical species, and adapting their mechanical properties to sustain necessary loads. Biological tissues achieve these desirable properties because of careful control over the contents, arrangements, and interconnections of individual cells, an approach that yields hierarchical materials with high levels of adaptability, responsiveness, and tunable mechanical strength. Replicating these types of emergent properties in synthetic materials remains a major engineering challenge. This Designing Materials to Revolutionize and Engineer our Future (DMREF) award supports basic research and scientific development of material systems that mimic the composition, organization, and properties of living tissues. The computationally led designs of tissues-like materials with precise compositions and spatial arrangements seek to offer a generalizable solution for applications in artificial tissue replacement, wound healing, soft robotics, and embedded computing technologies. In addition, the project will support the technical and professional development of the STEM workforce by promoting the participation of high school, undergraduate, and graduate students, especially from the first-generation and underrepresented groups, through various outreach and research activities.This project aims to study synthetic tissues comprised of independent cell-like compartments coupled hierarchically through mechanical tethering (i.e., self-assembling block copolymer microgels (BCPs) as synthetic cytoskeleton) and selective transport (i.e., protein-enriched biomimetic membranes (BMs) as selective barriers) mechanisms and incorporating stimuli-responsiveness (e.g., via polymers and membrane proteins) into the compartments. Computational approaches combine molecular transport, stimuli-responsive coupled deformations of BCPs, intercompartment adhesion, and biomembrane mechanics to predict failure behaviors, emergent properties, and functionalities of tissue-like assemblies. An iterative feedback loop between theory, computations, synthesis of BCPs, 3D bioprinting, and microscale mechanical characterization is central to the project for validating predictions, informing model development, and creating a modular database. The construction of a compartmentalized material system that exhibits selective internal transport pathways via lipid- and protein-based BMs and tunable mechanical properties via BCPs will be achieved by understanding how the tunable hydrophobic and hydrophilic regions of BCPs: 1) interact with amphiphilic BMs at the nanoscale; 2) self-assemble and entangle to form solid-like gels at the microscale; 3) cross-link between compartments at the macroscale to rigidify the entire assembly. Ultimately, this project will provide the quantitative knowledge base and modular design criteria to accelerate the assembly and use of compartmentalized tissue-like materials that are multifunctional, stimuli-responsive, adaptable, tough, and operate outside of equilibrium.This project is co-funded by the Division of Civil, Mechanical and Manufacturing Innovation in the Directorate for Engineering and the Division of Materials Research in the Directorate for Mathematical and Physical Sciences.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.