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

在自然界中，活细胞结合形成具有集体行为能力的组织，如感知和响应外部信号、交流、分类和储存化学物质，以及调整其机械特性以承受必要的负荷。生物组织实现这些理想的特性，是因为对单个细胞的内容、排列和相互连接进行了仔细的控制，这种方法产生了具有高水平适应性、响应性和可调机械强度的分层材料。在合成材料中复制这些类型的紧急特性仍然是一个重大的工程挑战。“设计材料以革新和工程我们的未来”（DMREF）奖支持模拟活组织的组成、组织和特性的材料系统的基础研究和科学发展。以计算为主导的类组织材料的设计具有精确的成分和空间安排，旨在为人工组织替代、伤口愈合、软机器人和嵌入式计算技术的应用提供一种通用的解决方案。此外，该项目将通过各种外展和研究活动，促进高中生、本科生和研究生的参与，特别是来自第一代和代表性不足群体的学生，从而支持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，这些隔室通过机械系结（即，自组装嵌段共聚物微凝胶（bcp）作为合成细胞骨架）和选择性运输（即，富含蛋白质的仿生膜（BMs）作为选择性屏障）机制分层耦合，并将刺激反应性（例如，通过聚合物和膜蛋白）纳入隔室。计算方法结合分子运输、bcp的刺激响应耦合变形、室间粘附和生物膜力学来预测组织样组件的失效行为、紧急特性和功能。理论、计算、bcp合成、3D生物打印和微尺度力学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核心。通过了解bcp可调节的疏水和亲水区域如何在纳米尺度上与两亲性BMs相互作用，构建一个通过脂质和蛋白质基BMs具有选择性内部运输途径和通过bcp可调节的机械性能的区隔材料系统将实现：2)在微观尺度下自组装缠绕形成固体状凝胶；3)在宏观尺度上，隔室之间的交联使整个装配体刚性。最终，该项目将提供定量知识库和模块化设计标准，以加速分区组织样材料的组装和使用，这些材料具有多功能、刺激响应性、适应性强、坚固性和非平衡性。该项目由工程理事会的土木、机械和制造创新司以及数学和物理科学理事会的材料研究司共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.