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

非技术描述为什么一棵树可以自我生长成复杂的形状，甚至可以在折断树枝后愈合，而家具则需要精心制作，损坏后才能修复？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“非生物”材料。仅仅是长出一张自我修复的桌子，不是很令人兴奋吗？生物学领域的最新发现和生物工程领域的发明表明，在不远的将来，这样的愿景可能会成为现实。为了实现这一目标，该项目将修改微观上的小细菌，使它们能够有选择地粘在一起，形成所需的宏观模式和结构--类似于不同颜色的乐高积木。由这种细菌生长的宏观生物材料的材料特性可以进行调整，例如，它们可以像木材一样硬，也可以像粘土一样更具延展性，甚至能够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/或智能地对外力做出反应。结合实验和模拟，研究人员将研究这种生物材料如何实现和编程。该项目还包括推广活动，使当地学童能够利用细菌和光线来培养和塑造这种细菌生物材料。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。在自然界中，许多细菌物种组成生物膜，执行复杂的协作功能，从化学物质的合成和运输到定向3D自组装和自修复。基于研究人员之前开发的合成细菌黏附素，该项目现在将把合成细胞-细胞黏附素逻辑与自我复制的成群细菌结合起来，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。该项目的结构分为四个目标：(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)将这种块形成具有不同瓷砖界面的子瓷砖的图案--以实现未来不同功能的空间分离，(Iii)开发能够预测这些细菌产生以所需方式图案的材料所需的起始条件的建模方法，以及(Iv)将这种块以合理的方式自组装成更大规模的3D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，在学校实施和评估此类生物材料的简化版本，重点是代表性不足的少数群体。学生们将自己制作简单的细菌材料并制作图案。此外，他们将用网络应用程序对这些系统的动态进行建模。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.