Shape-Morphing Living Composites

设计生物合成变形复合材料非技术摘要该奖项由材料研究部生物材料计划颁发给达拉斯的德克萨斯大学，旨在设计和表征由活细胞和非生物材料组成的变形复合材料。单细胞生物能够感知周围环境的微小变化，并对其做出反应，但在工程应用中很难将这些生物用作材料。相比之下，大多数合成材料不会对环境做出反应，或者只对非常大的变化做出反应，但这些材料的性能可以很容易地控制。这项研究工作将集中在混合材料的合成、3D打印和表征上，这种材料结合了生物和非生物成分的优点。具体地说，面包师的酵母将嵌入水凝胶中，水凝胶是一种主要由水组成的软材料。这些细胞的生长导致整个材料的形状发生变化。通过控制酵母的基因，在检测到环境中特定的微小变化后，可以建造材料来改变形状并产生特定的生物分子。这些材料可以用于简单的传感器，能够检测和报告体液或环境中的变化。这些新材料的行为还可以使药物输送设备能够感知肠道中的疾病状态，并通过向该地区输送治疗来做出反应。这项研究还将为K-12年级的学生创造机会，让他们了解生物学和材料科学的主题。技术摘要拟议工作的目标是利用微生物的受控增殖来创造能够编程改变形状的合成生物水凝胶。具体地说，酿酒酵母将被包埋在丙烯酰胺水凝胶中，这些细胞的增殖将导致复合材料的形状发生变化。与纯合成、响应性材料的工程学相比，这种方法的主要优势是基因工程和材料配方可以用来编程对预定的和令人难以置信的特定刺激的宏观复合反应。这项工作由四项研究任务组成：1)量化增殖诱导的复合材料形状变化过程中的局部和全局机械变形，并测量水凝胶力学性能对生长的影响；2)3D打印合成-活复合材料并测量几何形状和孔隙率对复合材料生长的影响；3)阐明剂量与响应之间的基本关系和活复合材料对代谢产物、蛋白质和光作为刺激引起形状变化的特异性；4)设计对酵母产生的酶反应可控的水凝胶基质，实现对形状变化的反馈控制。将测量酵母产生的代谢物、刺激物和蛋白质对整个复合体生长的影响，从而提供对支配生物材料的基本关系的理解。这项工作将解决对材料的迫切需求，这种材料可以感知高度特定的生化或微弱的物理线索，然后以受控的方式做出反应。这些材料将影响国家关键需求领域，包括可用于肠道的药物输送策略和简单的生化传感器。研究活动将与K-12学生在遗传学、水凝胶和酵母等主题上的推广工作相结合。这些努力将旨在增加未被充分代表的群体对科学事业的参与和研究的传播。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。

Designing Living-Synthetic, Shape-Morphing Composites Non-technical abstractThis award by the Biomaterials Program in the Division of Materials Research, to the University of Texas at Dallas, seeks to design and characterize shape-changing composites comprised of both living cells and non-living materials. Single-celled organisms sense and respond to very small changes in their surroundings, but it is difficult to use these organisms as materials in engineering applications. By comparison, most synthetic materials do not respond to their environment or only respond to very large changes, but the properties of these materials can be readily controlled. This research effort will focus on the synthesis, 3D printing, and characterization of hybrid materials that combine the advantages of both living and non-living components. Specifically, Baker's yeast will be embedded in a hydrogel, a soft material largely comprised of water. The growth of these cells causes the entire material to change in shape. By controlling the genes of the yeast, materials can be built to change shape and produce specific biomolecules after detecting specific, small changes in the environment. These materials may be used for simple sensors capable of detecting and reporting changes in bodily fluids or in the environment. The behavior of these new materials could also enable drug-delivery devices that sense disease states in the gut and respond by delivering treatment to the area. This research will also create opportunities for K-12 students to learn about topics in both biology and materials science. Technical abstractThe objective of the proposed work is to harness the controlled proliferation of microorganisms to create synthetic-living hydrogels capable of programmable shape change. Specifically, Saccharomyces cerevisiae will be embedded in acrylamide hydrogels, and the proliferation of these cells will induce shape change in the composite. The primary advantage of this approach, as compared to engineering purely synthetic, responsive materials, is that genetic engineering and material formulation can be used to program the macroscopic composite response to predetermined and incredibly specific stimuli. This work consists of four research tasks: 1) Quantify local and global mechanical deformation during proliferation-induced shape change of the composite and measure the effects of hydrogel mechanical properties on growth, 2) 3D print synthetic-living composites and measure the effects of geometry and porosity on composite growth, 3) Elucidate the fundamental relationship between dose and response and elucidate the specificity of living composites to metabolites, proteins, and light as stimuli that evoke shape change, and 4) Design hydrogel matrices that respond controllably to enzymes produced by the yeast, enabling feedback control of shape change. The effect of metabolites, stimuli, and proteins produced by the yeast on growth throughout the composite will be measured, thus providing understanding of the fundamental relationships that govern living materials. This work will address a critical need for materials that sense highly specific biochemical or weak physical cues and then respond in a controlled manner. These materials will impact areas of critical national need, including drug-delivery strategies that could be used in the gut and simple biochemical sensors. Research activities will be coupled to outreach efforts for K-12 students on topics including genetics, hydrogels, and yeast. These efforts will be aimed at both increasing participation of underrepresented groups in science careers and dissemination of research.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.