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

为什么一棵树可以自我生长成复杂的形状，折断一根树枝甚至可以自愈，而一个人的家具需要精心制作，损坏后需要修复？像这样的问题指引着“可编程生物材料”的未来愿景——超越人类几千年来一直使用的传统“无生命”材料。种植一张能自我修复的桌子不是很令人兴奋吗？生物学的最新发现和生物工程领域的发明表明，这样的愿景可能在不久的将来成为现实。为了实现这一目标，该项目将修改微小的细菌，使它们能够选择性地粘在一起，形成所需的宏观模式和结构——类似于不同颜色的乐高积木。从这种细菌中生长出来的宏观生物材料的材料特性可以被调整，例如，它们可以像木头一样坚硬，也可以像粘土一样更具延展性，它们甚至可以在硬和软之间快速变化。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，使当地学校的孩子能够利用细菌和光来生长和塑造这种细菌生物材料。技术描述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目前非常有限。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，从化学物质的合成和运输到定向3D自组装和自我修复。基于先前由研究人员开发的合成细菌粘附素，该项目现在将把合成细胞-细胞粘附素逻辑与自我复制的群集细菌结合起来，并为可编程生物材料奠定基础。该团队结合了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，以控制细菌细胞的沉积和组装，以产生“材料块”；（ii）将这些块图案成具有不同瓷砖界面的子砖，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所需材料的起始条件，以所需的方式形成图案。（iv）将这些块以合理的方式自组装成更大的三维生物材料。研究人员还将与当地科学教师和教育专业人员合作，在学校实施和评估这种生物材料的简单版本，重点关注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，他们还将用web applet对这些系统进行动态建模。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。

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.