Development of Gold Nanoparticle based Photo-responsive Inorganic Prototissues

1957年，托马斯明瑞·张博士首次提出了人工细胞或原始细胞的概念，通过研究非生物细胞类似物，为研究人员提供了对原始细胞功能和行为的更深入了解。原细胞是合成的细胞样微区室，其被设计成模拟活细胞的关键方面，例如自发生长和分裂、吞噬作用和基因指导的蛋白质合成，仅举几例。在过去的十年中，基于脂质囊泡、自组装聚合物、无机胶体微胶囊（胶体体）、半渗透性蛋白质-聚合物纳米缀合物等，已经开发了一系列不同的合成原始细胞模型。许多研究团队目前正专注于通过使用自上而下的方法来提高这些材料的生物功能性和自主性水平。Pierangelo Gobbo博士的研究小组通过利用生物正交点击化学将原始细胞共价组装成组织样结构（称为prototissues），在该领域取得了显着的进展。这些化学上相互关联的原组织显示集体热调节收缩性，可以酶促调制和利用机械化学转导。最重要的是，这项工作允许第一个合成路线来制造能够集体行为的组织样材料。在不同的原始细胞模型中，无机胶体体由于其与生物对应物相比的相关益处而受到越来越多的关注，例如增加化学，热和机械鲁棒性。虽然无机原生细胞膜已经由二氧化硅或磁性纳米颗粒制备，但功能性金纳米颗粒（AuNPs）的使用基本上仍未被探索。AuNP界面可以被设计成经历过多的界面、生物正交、点击反应，用于在复杂环境中化学选择性捕获和释放互补分子系统。本研究旨在制造聚合物包覆的AuNPs作为能够自组装成功能性金胶体体的简单构建块。AuNP的光响应性质允许通过表面等离子体共振将光转换成局部热，从而触发涂覆AuNP的热响应聚合物的较低临界溶解温度。然后，这些原始细胞可以共价交联成原始组织，能够集体光调节收缩性，可以酶促调节。该项目的核心目标是探索生命物质和非生命物质之间的界面，并开创性地取得突破性的科学进展，从基于AuNP的胶体体构建块中生成原细胞材料。该研究项目是高度多学科的，冒险的，旨在通过首次将功能纳米材料领域与原细胞生物设计和构建方面合并，开辟自下而上合成生物学的新前沿。这项拟议中的研究有望产生第一种无机的原细胞材料，可用于光热治疗、生物传感和药物输送。该项目由布里斯托大学和西安大略大学通过cotutelle项目联合进行，福尔斯属于EPSRC物理科学（合成生物学）研究领域。

First proposed by Dr. Thomas Ming Swi Chang in 1957, the concept of artificial cells, or protocells, serves to provide researchers with deeper insights into primitive cellular functions and behaviours through the study of abiotic cellular analogues. Protocells are synthetic, cell-like microcompartments designed to mimic key aspects of living cells, such as spontaneous growth and division, phagocytosis, and gene-directed protein synthesis, to name a few. In the past decade, a range of different synthetic protocell models have been developed based on lipid vesicles, self-assembled polymers, inorganic colloidal microcapsules (colloidosomes), semi-permeable protein-polymer nano-conjugates, and more. Many research teams are currently focusing on increasing the levels of bio-functionality and autonomy of these materials by advancing the protocells biochemical complexity using top-down methodologies. The research group of Dr. Pierangelo Gobbo have made remarkable steps forward in the field through utilizing bioorthogonal click chemistry to covalently assemble protocells into tissue-like constructs, termed prototissues. These chemically interlinked prototissues display collective thermally regulated contractibility that can be enzymatically modulated and exploited for mechanochemical transduction. Most importantly, this work allowed for the first synthetic route to fabricate tissues-like materials capable of collective behaviours.Among the different protocell models, inorganic colloidosomes are receiving growing attention due to their relevant benefits compared to their biological counterparts, such as increased chemical, thermal and mechanical robustness. While inorganic protocell membranes have been prepared from silica or magnetic nanoparticles, the use of functional gold nanoparticles (AuNPs) remains essentially unexplored. AuNP interfaces can be engineered to undergo a plethora of interfacial, bio-orthogonal, click reactions for the chemo-selective capture and release of complementary molecular systems in complex environments. This research aims to fabricate polymer-coated AuNPs as simple building blocks capable of self-assembly into functional gold colloidosomes. The photo-responsive nature of AuNPs allows for light conversion into localized heat through surface plasmon resonances, triggering the lower critical solution temperature of the thermo-responsive polymers coating the AuNPs. These protocells can then be covalently cross-linked into prototissues, capable of collective photo-regulated contractibility that can be enzymatically modulated. The goal of this project at its core is to explore the interface between living matter and non-living matter and pioneering ground-breaking scientific advancements towards the generation of protocellular materials from AuNP-based colloidosome building blocks. This research project is highly multidisciplinary, adventurous and aims to open new frontiers in bottom-up synthetic biology by merging for the first time the field of functional nanomaterials with aspects of protocellular bio-design and construction. The proposed research is expected to lead to the first inorganic, protocellular materials that could be employed for applications in photothermal therapy, biosensing, and drug delivery. This project is joint between the University of Bristol and the University of Western Ontario through a cotutelle program and falls within the EPSRC physical sciences (synthetic biology) research area.