Collaborative Research: Foundations of programmable living materials through synthetic biofilm engineering and quantitative computational modeling

合作研究：通过合成生物膜工程和定量计算建模为可编程生物材料奠定基础

• 批准号: 2214020
• 负责人: Hans Riedel-Kruse
• 金额: $ 30.73万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2025-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2214020&HistoricalAwards=false
• 关键词: Collaborative; Research; Foundations; programmable; living

Non-technical descriptionWhy can a tree self-grow into a complex shape and even heal if you break off a branch, while one’s furniture needs to be crafted and be repaired when damaged? Questions like this guide the future vision of ‘programmable biomaterials’ – moving beyond the traditional ‘nonliving’ materials humans have been utilizing for millennia. Wouldn’t it be exciting to just grow a self-healing table? Recent discoveries in biology and inventions in the field of bioengineering suggest that such a vision could become a reality in the not-too-distant future. Toward this goal, this project will modify microscopically small bacteria so that they can selectively stick together in desired macroscopic patterns and structures – similarly to differently colored Lego Bricks. The materials properties of macroscopic biomaterials grown from such bacteria can then be to tuned, for example, they could be hard like wood or more malleable like clay, and they could even be able to rapidly change between hard and soft. And then there are the truly novel biomaterials aspects: As these cells can still divide and grow and move – this macroscopic material could then change its shape and/or intelligently respond to external forces. Combining experiments and simulations, the researchers will investigate how such biomaterials can be realized and programmed. This project also includes outreach activities that will enable local school children to use bacteria and light in order to grow and pattern such bacterial biomaterials.Technical descriptionThe ability to engineer functional multicellular biomaterial is currently very limited as suitable biomaterial components and self-assembly algorithms are lacking. In nature, many bacterial species organize into biofilms that perform complex cooperative functions, ranging from synthesis and transport of chemicals to directed 3D self-assembly and self-repair. Based on previously synthetic bacterial adhesins developed by the researchers, this project will now integrate a synthetic cell-cell adhesin logic with self-replicating swarming bacteria and establish the foundation for programmable biomaterials. The team combines biophysical modeling and synthetic biology to study these multicellular materials. The project is structured in four aims: (i) Development of bioengineering tools to enable control over deposition and assembly of bacterial cells to generate ‘material blocks’, (ii) patterning of such blocks into sub-tiles with distinct tile-interfaces in between – in order to achieve future spatial separation of different functions, (iii) develop modeling approaches that can predict the starting conditions required for these bacteria to generate a material that is patterned in the desired way, and (iv) take such blocks and have them self-assemble in a rational manner into larger-scale 3D living materials. The researchers will work also with local science teachers and educational professionals to implement and evaluate the use of simpler versions of such biomaterials in schools with a focus on underrepresented minorities. The students will fabricate and pattern simple bacterial materials themselves. Furthermore, they will model the dynamics if these systems with a web applet.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.

非技术性描述为什么一棵树可以自行长成复杂的形状，甚至在折断树枝后可以愈合，而家具在损坏时需要制作和修复？这样的问题引导了“可编程生物材料”的未来愿景——超越人类已经使用了数千年的传统“非生命”材料，仅仅种植一个自我修复的桌子不是很令人兴奋吗？为了实现这一目标，这个愿景可能在不久的将来成为现实，该项目将修改微观的小细菌，使它们能够选择性地以所需的宏观图案和结构粘在一起——类似于不同颜色的乐高积木的材料特性。然后，可以对由此类细菌生长的宏观生物材料进行调整，例如，它们可以像木材一样坚硬，也可以像粘土一样具有可塑性，甚至可以在硬和软之间快速变化，然后才是真正新颖的生物材料。方面：由于这些细胞仍然可以分裂、生长和移动——这种宏观材料可以改变其形状和/或智能地响应外力，研究人员将研究如何实现和编程这种生物材料。外展活动将使当地学童能够利用细菌和光来培养和图案化此类细菌生物材料。技术描述目前，由于缺乏合适的生物材料组件和自组装算法，设计功能性多细胞生物材料的能力非常有限。许多细菌物种组织成生物膜，执行复杂的协作功能，从化学物质的合成和运输到定向 3D 自组装和自我修复，基于研究人员先前开发的合成细菌粘附素，该项目现在将整合一种合成细胞-该团队结合生物物理模型和合成生物学来研究这些多细胞材料，其目的是利用细胞粘附素逻辑与自我复制的群聚细菌，并为可编程生物材料奠定基础。生物工程工具能够控制细菌细胞的沉积和组装，以生成“材料块”，(ii) 将这些块图案化为子块，其间具有不同的块界面——以实现未来不同功能的空间分离， (iii) 开发建模方法，可以预测这些细菌生成以所需方式图案化的材料所需的起始条件，以及 (iv) 采用这些块并让它们以合理的方式自组装成更大规模的 3D研究人员将研究生活材料。还与当地科学教师和教育专业人员合作，在学校中实施和评估此类生物材料的简单版本，重点关注代表性不足的少数群体。此外，他们还将对这些系统的动态进行建模。该奖项反映了 NSF 的法定使命，并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，被认为值得支持。