The impact of metals and metal based nanoparticles on model membranes and complex biological systems

金属和金属基纳米颗粒对模型膜和复杂生物系统的影响

• 批准号: RGPIN-2018-03911
• 负责人: Prenner, Elmar
• 金额: $ 3.06万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=662594
• 关键词: impact; metals; metal; based; nanoparticles

My long-term research focus is on the role of lipids in the structure and function of biological membranes. This proposal aims at understanding how external binding partners modulate the structure and function of biomembranes. More specifically, the impact of environmental pollutants on key factors like membrane fluidity and permeability will be addressed.****Using state-of-the-art biophysical methods, the interactions of model lipid membranes with toxic heavy metals cadmium, mercury and lead with be characterized. The studies will also include transition metals cobalt, nickel, copper and manganese. Moreover, metal mixtures will be examined as biological systems are usually exposed to more than one metal at a time, and metal combinations can have stronger effects. The broad screen of lipid classes varying in structure and side chain composition provides a database allowing the analysis results from complex membrane extracts, intact biomemebranes and organelles.****Considering that metal nanoparticles are increasingly released into the environment and taken up by the lungs, their impact on lung surfactant models will be assessed as well. Finally, the results obtained from mimetic systems will be used to design experiments involving complex biological membrane extracts, organelles, and blood cells, which are a primary metal target in the bloodstream.****This work will help to better understand the mechanisms of metal toxicity by identifying lipids that are targeted in biomembranes. Moreover, the assessment of metal nanoparticles is of utmost relevance as insufficient data still limits our understanding of nanotoxicology. Ultimately, the outcomes of these investigations will advance our knowledge on disease mechanisms and will help to improve treatments and prevention strategies. In addition, it will aid in the establishment of effective handling guidelines for nanoparticle production.*********

我的长期研究重点是脂质在生物膜结构和功能中的作用。这项建议旨在了解外部结合伙伴如何调节生物膜的结构和功能。更具体地说，将讨论环境污染物对膜流动性和通透性等关键因素的影响。*使用最先进的生物物理方法，表征模型类脂膜与有毒重金属镉、汞和铅的相互作用。这些研究还将包括过渡金属钴、镍、铜和锰。此外，由于生物系统通常一次接触一种以上的金属，因此将对金属混合物进行检查，而金属组合可能具有更强的影响。不同结构和侧链组成的脂类的广泛筛选提供了一个数据库，允许对复杂的膜提取物、完整的生物膜和细胞器的分析结果。*考虑到金属纳米颗粒越来越多地释放到环境中并被肺部吸收，也将评估它们对肺表面活性物质模型的影响。最后，从模拟系统中获得的结果将被用于设计涉及复杂生物膜提取物、细胞器和血细胞的实验，这些细胞是血流中的主要金属靶标。*这项工作将有助于通过识别生物膜中的靶向脂类来更好地了解金属毒性的机制。此外，对金属纳米颗粒的评估具有极其重要的意义，因为数据不足仍然限制了我们对纳米毒理学的理解。归根结底，这些调查的结果将增进我们对疾病机制的了解，并将有助于改进治疗和预防战略。此外，它还将有助于建立有效的纳米颗粒生产处理指南。