Force-sensing artificial cells and tissues with synthetic DNA mechanotransducers.

人工细胞是能够复制类似生命行为的微米级合成实体，具有从生产相关生物分子到智能治疗诊断学的巨大潜力。自下而上的合成生物学旨在开发一个产生它们的平台，但目前面临着一个瓶颈：缺乏环境感知和通信能力，从而限制了细胞的有前途的功能。特别令人感兴趣的是，没有用于实现机械感测的方法，而机械感测对于产生具有下一代智能植入物和体内治疗平台中的潜在应用的响应性人工组织至关重要。DNA纳米技术提供了前所未有的控制和结构及其动力学的可编程性;后者加上其易于功能化和生物相容性，使DNA纳米结构成为模拟生物机械的理想选择。这个博士旨在构建一类新型的全合成的基于DNA的膜锚定机械换能器，其可以在人工细胞和响应性人工组织上实现。通过将膜张力的变化与脂质相分离相结合，这些anotensors将在人工细胞的细胞质中诱导生物化学过程，例如蛋白质产生和DNA反应级联，最终为人工细胞中的工程机械传感提供平台。

Artificial cells, micron-sized synthetic entities capable of replicating life-like behaviours, have a great potential spanning from the production of relevant biomolecules to smart theranostics. Bottom-up synthetic biology aims to develop a platform for generating them, but currently faces a bottleneck: the lack of environmental-sensing and communication capabilities, thereby restricting the promising functionalities of the cells. Of particular interest, there is no approach for implementing mechanosensing, which in turn is critical for the generation of responsive artificial tissues with potential applications in next generation smart implants and in vivo therapeutic platforms. DNA Nanotechnology offers unprecedented control and programmability of structures and their dynamics; the latter coupled to their ease of functionalisation and biocompatibility make DNA nanoconstructs ideal for mimicking biological machinery. This Ph.D. aims at constructing a novel class of fully synthetic DNA-based membrane-anchored mechanotransducers that can be implemented on artificial cells and responsive artificial tissues. By coupling changes in membrane tension with lipid phase separation, these anotransducers will induce biochemical processes in the cytoplasm of artificialcells such as protein production and DNA reaction cascades, ultimately providing a platform for engineering mechanosensing in artificial cells.