Nonlinear optical microtomography of biological structures

生物结构的非线性光学显微断层扫描

基本信息

批准号：
261416-2012
负责人：
Barzda, Virginijus
金额：
$ 1.82万
依托单位：
University of Toronto
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2016
资助国家：
加拿大
起止时间：
2016-01-01 至 2017-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=594554
关键词：
Nonlinear optical microtomography biological structures

项目摘要

Nonlinear optical (NLO) microscopy is a noninvasive imaging modality that is rapidly gaining in popularity due to its ability to visualize label free noncentrosymmetrically organized molecular aggregates and interfaces in biological structures. In addition to employing signal intensity as a contrast mechanism, biological samples can be investigated using spectroscopic and polarization measurements of nonlinear signals in the microscope revealing molecular organization of the visualized structures. Combination of the polarization and spectroscopic imaging methods with ab initio calculations of nonlinear optical properties of biomolecules renders a powerful structural investigation tool that provides possibility to reconstruct molecular organization of the highlighted structures. Therefore, we propose to develop nonlinear optical microtomography method to study molecular structure of biological crystals and ordered aggregates. The NLO microtomography will be based on nonlinear microscopy measurements of second harmonic generation (SHG) and vibrational sum frequency generation (V-SFG). The obtained information about molecular organization will be used to study collagen and myosin fibrils, amyloid aggregates, as well as starch granules and cellulose fibrils. The fundamental understanding about the nonlinear optical properties of proteins and polysaccharides will help to advance several application areas: The collagen structural properties and content are linked to the development of cancer, therefore NLO imaging of collagen will provide with method for noninvasive cancer diagnostics in vivo. Dynamic imaging of myosin structure in muscles during contraction will enable to study contractility mechanisms of the nanomotors and will aid in studying cardiac arrhythmias and various types of myopathies. The study of amyloid structures will help to understand the toxicity of aggregates involved in progression of the neurodegenerative disorders. Investigations of synthesis and degradation of starch granules and cellulose fibers will provide basis for using nonlinear microscopy in food, pulp and paper industry for quality control of pharmaceuticals, paper, biodegradable plastics, and biofuel.

非线性光学（NLO）显微镜是一种非侵入性成像方式，由于其能够可视化生物结构中的无标记非中性分子聚集体和界面，因此它迅速流行。除了采用信号强度作为对比机制外，还可以使用显微镜中非线性信号的光谱和极化测量来研究生物样品，从而揭示了可视化结构的分子组织。极化和光谱成像方法的结合与生物分子非线性光学特性的概念计算相结合，这是一个强大的结构研究工具，提供了重建突出显示结构的分子组织的可能性。因此，我们建议开发非线性光学显微学方法，以研究生物晶体和有序聚集体的分子结构。 NLO显微镜图将基于第二次谐波生成（SHG）和振动总和频率产生（V-SFG）的非线性显微镜测量值。获得的有关分子组织的信息将用于研究胶原蛋白和肌球蛋白原纤维，淀粉样蛋白聚集体以及淀粉颗粒和纤维素原纤维。对蛋白质和多糖的非线性光学特性的基本理解将有助于推进几个应用领域：胶原蛋白结构特性和内容与癌症的发展有关，因此，胶原蛋白的NLO成像将提供无侵袭性癌症诊断的方法。收缩期间肌肉肌球蛋白结构的动态成像将使纳米运动器的收缩力机制有助于研究心律不齐和各种类型的肌病。淀粉样结构的研究将有助于理解与神经退行性疾病进展有关的聚集体的毒性。对淀粉颗粒和纤维素纤维的合成和降解的研究将为使用非线性显微镜在食品，纸浆和造纸工业中提供质量控制药物，纸张，可生物降解塑料和生物燃料的基础。