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: 2214021
• 负责人: Joern Dunkel
• 金额: $ 21.18万
• 依托单位: Massachusetts Institute of Technology
• 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=2214021&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.

非技术性的修复为什么一棵树可以自行长成复杂的形状，甚至可以在你折断一根分支时愈合，而一个人的家具需要手工制作，在损坏时修复？像这样的问题指导着“可编程生物材料”的未来愿景-超越人类数千年来一直使用的传统“非生命”材料。如果能种出一张自我修复的桌子，不是很令人兴奋吗？最近在生物学领域的发现和生物工程领域的发明表明，这样的愿景可能在不太遥远的将来成为现实。为了实现这一目标，该项目将修改显微镜下的小细菌，使它们能够选择性地以所需的宏观模式和结构粘在一起-类似于不同颜色的乐高积木。然后可以调整从这种细菌生长的宏观生物材料的材料特性，例如，它们可以像木材一样坚硬，或者像粘土一样更具延展性，并且它们甚至可以在坚硬和柔软之间快速变化。然后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。结合实验和模拟，研究人员将研究如何实现和编程这种生物材料。该项目还包括外展活动，使当地学童能够使用细菌和光来培养和塑造这种细菌生物材料。技术支持由于缺乏合适的生物材料成分和自组装算法，目前设计功能性多细胞生物材料的能力非常有限。在自然界中，许多细菌物种组织成生物膜，执行复杂的合作功能，从合成和运输化学物质到定向3D自组装和自修复。基于研究人员先前开发的合成细菌粘附素，该项目现在将合成细胞-细胞粘附素逻辑与自我复制的群集细菌相结合，并为可编程生物材料奠定基础。该团队结合生物物理建模和合成生物学来研究这些多细胞材料。该项目有四个目标：（i）开发生物工程工具，以便能够控制细菌细胞的沉积和组装，从而产生“材料块”，（ii）将这些块图案化为子瓦片，在子瓦片之间具有不同的瓦片界面，以便实现未来不同功能的空间分离，（iii）开发建模方法，其可以预测这些细菌产生以所需方式形成图案的材料所需的起始条件，以及（iv）采用这种块并使它们以合理的方式自组装成更大规模的3D活体材料。研究人员还将与当地的科学教师和教育专业人士合作，实施和评估在学校中使用这种生物材料的简单版本，重点是代表性不足的少数民族。学生们将自己制作简单的细菌材料。此外，他们将模拟动态，如果这些系统与一个网络applet。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。