High-throughput quantification of the interactions between biomolecules and cells with engineered surfaces

通过工程表面对生物分子和细胞之间的相互作用进行高通量定量

• 批准号: RGPIN-2014-03829
• 负责人: Nicolau, Dan
• 金额: $ 1.46万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=566114
• 关键词: throughput; quantification; interactions; between; biomolecules

The study of the complex behaviour of biological systems often asks for a large scale experimentation approach, to comprehensively describe their responses to a large variety of perturbation parameters. In the last decades, this large scale experimentation approach has been made possible due to the miniaturisation of biochemical and (more recently) cell-based tests. While these techniques present a certain degree of empirical, `brute force' probing of the systems studied, the ultimate goal of this powerful methodology is the prediction of the behavior of biological systems based on the deciphering the underlying mechanisms, rather than the prediction based on empirical observation. Usually, large scale experimentation has been used for `omics' applications, e.g., genomics, proteomics, metabolomics, for the benefits of drug discovery, but the methodology has been used for other applications, e.g., the discovery of new materials and biomaterials. To this end, the long term objective of the proposed program is to progress the understanding-based prediction of the behavior of hybrid systems comprising biomolecules, in particular proteins; and cells, in particular microorganisms, interfaced with artificial surfaces and structures. This objective will be fulfilled through a programmatic progression from (i) large scale, standardized experimentation yielding comprehensive empirical data; to (ii) construction of semi-empirical correlations between the parameters of the biological component, i.e., biomolecule, cell; and those of the artificial component, i.e., surfaces, micro/nano-structures; to (iii) model-based predictions of the behavior of the systems of interest; thus allowing for engineering-style design, fabrication and operation of hybrid bio-nano-devices.In the short term, the program aims to (i) develop an experimental platform that integrates microfluidics, microarrays, biosensors and MEMS elements for the combinatorial study of interactions of biomolecules and cells with engineered surfaces; (ii) collect data regarding protein adsorption and bioactivity from large scale, standardized experimentation; and find statistical relationships regarding protein adsorption between protein properties; surface properties; and fluid properties; (iii) derive design rules for nano-structured surfaces specifically interfacing individual protein molecules; and (iv) demonstrate the quantification of the motility of biological systems, i.e., cytoskeletal proteins and motile microorganisms, as an ultimate reporter of the bioactivity of the system interfacing artificial structures and surfaces.The program deliverables are linked to various levels of impact. Firstly, the methodological advances will demonstrate the use of the integrated combinatorial-testing device, which will help the standardization and efficiency of relevant studies in the area of microbiology, drug discovery, diagnostics and fundamental molecular biology studies. Second, the fabrication of structures that induce a specific biological behavior, e.g., antifouling, selective adsorption, bioactivity preservation, will impact on areas as diverse as surgical instruments, implants, diagnostic devices, consumer products, food processing, air conditioning equipment, antifouling of ships, etc. Considering biomaterials only (a $8bn market), the possibility of quick "design & test" of personalised biomaterials will greatly amplify the capacity of addressing the patient's, rather than a generic medical condition. Third, the quick and comprehensive quantification of the motility of cytoskeleton filaments and microorganisms, on drug discovery for e.g., cancer, neurodegenerative diseases; or new, virulent hospital-based infectious diseases - a particular problem for Canada.

生物系统复杂行为的研究往往需要大规模的实验方法，以全面描述它们对各种扰动参数的响应。在过去的几十年里，由于生物化学和（最近）基于细胞的测试的简化，这种大规模的实验方法已经成为可能。虽然这些技术提出了一定程度的经验，“蛮力”的系统研究的探测，这种强大的方法的最终目标是预测的基础上破译的潜在机制的生物系统的行为，而不是预测的基础上的经验观察。通常，大规模实验已用于“组学”应用，例如，基因组学、蛋白质组学、代谢组学，用于药物发现的益处，但是该方法已经用于其它应用，例如，新材料和生物材料的发现。为此，拟议计划的长期目标是推进对混合系统行为的基于理解的预测，该混合系统包括生物分子，特别是蛋白质;和细胞，特别是微生物，与人工表面和结构连接。这一目标将通过从（i）产生全面经验数据的大规模标准化实验到（ii）构建生物组分参数之间的半经验相关性的程序性进展来实现，即，生物分子、细胞;以及人工组分的那些，即，在短期内，该计划的目标是：（i）开发一个实验平台，将微流体、微阵列、生物传感器和MEMS元件集成在一起，用于生物分子和细胞与工程表面相互作用的组合研究;（ii）从大规模标准化实验中收集关于蛋白质吸附和生物活性的数据;并找到关于蛋白质性质、表面性质和流体性质之间的蛋白质吸附的统计关系;（iii）导出用于纳米结构表面的设计规则，所述纳米结构表面特异性地与单个蛋白质分子接合;以及（iv）证明生物系统的运动性的量化，即，细胞骨架蛋白和能动微生物，作为人工结构和表面界面系统生物活性的最终报告者。首先，方法学的进步将展示集成组合测试设备的使用，这将有助于微生物学，药物发现，诊断和基础分子生物学研究领域的相关研究的标准化和效率。第二，诱导特定生物行为的结构的制造，例如，吸附、选择性吸附、生物活性保存将影响手术器械、植入物、诊断设备、消费品、食品加工、空调设备、船舶维修等领域。（一个80亿美元的市场），个性化生物材料的快速“设计和测试”的可能性将大大增强解决患者，而不是一般的医疗状况。第三，细胞骨架细丝和微生物的运动性的快速和全面的定量，例如，癌症、神经退行性疾病;或新的、致命的医院传染病--这是加拿大的一个特殊问题。