Development of Gold Nanoparticle based Photo-responsive Inorganic Prototissues

1957年，张明瑞博士首次提出了人工细胞或原细胞的概念，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。原细胞是一种合成的细胞样微室，旨在模仿活细胞的关键方面，如自发生长和分裂、吞噬作用和基因导向的蛋白质合成等。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）、半透性蛋白质-聚合物纳米偶联物等，已经开发了一系列不同的合成原始细胞模型。目前，许多研究团队正致力于通过自上而下的方法提高原始细胞的生化复杂性，从而提高这些材料的生物功能和自主性水平。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（称为原始组织），在该领域取得了显著进展。这些化学上相互联系的原始组织显示出集体热调节的收缩能力，可以被酶调节并用于机械化学转导。最重要的是，这项工作为制造具有集体行为的类组织材料提供了第一个合成途径。在不同的原始细胞模型中，无机胶体体由于其与生物胶体体相比的相关优势而受到越来越多的关注，例如增加了化学，热和机械稳健性。虽然无机原始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）的使用基本上尚未探索。AuNP界面可以被设计成经历大量的界面、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被的AuNPs作为能够自组装成功能性金胶体体的简单构建块。aunp的光响应特性允许光通过表面等离子体共振转换为局部热，从而触发覆盖在aunp上的热响应聚合物的较低临界溶液温度。然后这些原始细胞可以共价交联成原始组织，具有集体光调节的收缩能力，可以被酶调节。该项目的核心目标是探索生物物质和非生物物质之间的界面，并在以aunp为基础的胶体体构建块生成原细胞材料方面取得突破性的科学进展。该研究项目是高度跨学科的，具有冒险精神，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相结合，开辟自下而上合成生物学的新领域。这项研究预计将导致第一个无机的、原细胞材料，可用于光热治疗、生物传感和药物输送。该项目由布里斯托尔大学和西安大略大学通过cotutelle项目联合开展，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.