Engineering motile artificial cells capable of swimming up concentration gradients

数十亿年的进化将细胞塑造成高度复杂的微型机器，其复杂的分子相互作用网络很难解开。自下而上的合成生物学旨在通过将少量分子制剂组合到分隔的微环境中来构建人工细胞。这种还原论的方法可以在简化的环境中研究生物过程。然而，更重要的是，它提供了生产智能细胞样制剂的机会，以解决诊断、治疗、生物合成和生物修复方面的迫切需求。大多数试图将类似生命的“行为”植入人造细胞的尝试都集中在新陈代谢、能量产生、计算和通信上。到目前为止，一个被忽视的行为是运动性：指向目标部位的定向运动。运动性（例如游泳和爬行）是所有生命类别中都存在的特征：从执行垂直迁移的单细胞光合生物到优化光照，游动的精子细胞和追捕病原体的巨噬细胞。在大多数情况下，细胞能够根据环境线索指导它们的运动，通常是光强度（趋光性）、温度（热趋向性）或化学物质浓度（趋化性）的梯度。尽管在大多数可预见的人造细胞应用中，可控的出租车将带来无可置疑的好处，但在合成细胞中进行工程运动的可行技术尚未开发出来。这是因为驱动运动所需的蛋白质组件（例如鞭毛）是存在的最复杂的大分子结构，并且使用当前的技术状态将它们重组为合成系统是根本不可能的。在这个项目中，我们将开发一种细胞仿生学解决方案来应对这一挑战：我们将开发基于DNA生物物理学的新型纳米技术，以推动合成细胞向前发展，提高浓度梯度，并在细胞到达目标位点时引发反应（蛋白质合成）。

Billions of years of evolution shaped cells into highly sophisticated micromachines, whose intricate network of molecular interactions are difficult to unravel. Bottom-up synthetic biology aims at constructing artificial cells by combining a small number of molecular agents into compartmentalised microenvironments. This reductionist approach enables the study of biological processes in a simplified setting. More importantly however, it offers the opportunity of producing smart cell-like agents to tackle pressing needs in diagnostics, therapeutics, biosynthesis, and bioremediation. Most attempts at engineering life-like 'behaviours' into artificial cells have focused on metabolism, energy generation, computation, and communication. One behaviour which has been neglected so far is motility: directed motion towards a target site. Motility (e.g. swimming and crawling) is a characteristic that is found across all life classes: from unicellular photosynthetic organisms that perform vertical migrations to optimise light exposure, swimming sperm cells, and macrophages that chase down pathogens. In most instances, cells are able to direct their motion following environmental cues, typically gradients in light intensity (phototaxis), temperature (thermotaxis), or the concentration of chemicals (chemotaxis). Despite the unquestionable benefits that controllable taxis would bring for most foreseen applications of artificial cells, viable technologies for engineering motion in synthetic cells have not been developed. This is because the protein assemblies needed to drive motility (e.g. flagella) are the most complex macromolecular structures in existence, and reconstituting them into synthetic systems is simply not possible using current state of the art. In this project we will develop a cellular bionics solution to this challenge: instead of using native cellular machineries, we will develop novel nanotechnologies based on DNA biophysics to propel a synthetic cell forwards, up a concentration gradient, with cell engineered to elicit a response (protein synthesis) when reaching its target site.