Nanoshell sensors for cellular analysis

用于细胞分析的纳米壳传感器

• 批准号: 9307921
• 负责人: CRAIG A ASPINWALL
• 金额: $ 29.67万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307921
• 关键词: Architecture; Area; Bioavailable; Biodistribution; Biological Availability; Biosensor; Carbohydrates; Categories; Cells; Charge; Chemicals; Chemistry; Complex; Coupling; Detection; Development; Diabetes Mellitus; Dialysis procedure; Diffusion; Drug Delivery Systems; Elements; Encapsulated; Engineering; Environment; Enzymes; Epidemic; Ethnic Origin; Fluorescence Resonance Energy Transfer; Future; Geometry; Glucagon; Glucose; Health; Healthcare; Human; Incidence; Insulin; Insulin Resistance; Investigation; Ion Channel; Lipids; Measurement; Membrane; Metabolic; Modification; Molecular; Molecular Weight; Monitor; Neuroendocrine Cell; Non-Insulin-Dependent Diabetes Mellitus; Optics; Pancreas; Pathway interactions; Peptide Hydrolases; Peptides; Performance; Permeability; Phospholipids; Physiological; Phytic Acid; Plant Roots; Polymers; Process; Proteins; Pyruvate; Quality of life; Regulation; Reporter; Research Project Grants; Role; Route; S-1 Antimetabolite agent; Scheme; Series; Serum; Signal Pathway; Signal Transduction; Silicon Dioxide; Societies; Solid; Structure of alpha Cell of islet; Surface; System; Technology; Testing; Thick; Toxic effect; Transducers; Vesicle; Wages; age group; aptamer; aqueous; biomaterial compatibility; cell type; cost; design; extracellular; improved; innovation; insulin secretion; monomer; nanoscale; nanosensors; nanoshell; non-diabetic; novel; optical sensor; pancreatic juice; passive transport; polymerization; public health relevance; scaffold; sensor; small molecule; uptake

 DESCRIPTION (provided by applicant): The incidence of diabetes mellitus has reached epidemic proportions in the U.S. and will continue to increase rapidly across all age group and ethnicities for the foreseeable future. The resulting cost to society via health care, lost wages, etc. is staggering and the decreased quality of life is immeasurable. Type 2 diabetes is primarily manifest in two categories, insufficient insulin secretion and enhanced insulin resistance. In non-diabetics, increased serum glucose stimulates insulin secretion from the pancreatic -cell and decreases glucagon secretion from the pancreatic -cell. Glucose-stimulated insulin secretion is a complex process that is regulated via complex signaling pathways within the cell. The dynamics of cellular signaling, and corresponding insulin release, are critical to normal regulation of serum glucose, however, detection of many cellular signals is not possible due to a dearth of sensing technologies. Recent studies have "rediscovered" the importance of the -cell in regulating serum glucose, however much less is understood regarding the dynamics of metabolic signaling in -cells. A better understanding of intracellular signaling and corresponding regulated release within both of these cell types is of paramount importance to elucidate the root causes of secretory abnormalities and the corresponding roles in the onset and progression of diabetes. The primary focus of this proposal is to develop suitable capabilities to monitor metabolic and carbohydrate-derived signals in - and -cells, and to facilitate identification of key molecular differences that may contribute to diabetes. We will develop, characterize and utilize a highly-stable, porous phospholipid architecture with enhanced mass transport capabilities for detection of intracellular regulators that lack intrinsic optical or electrochemical activity. Phospholipid scaffolds are prepared with ca. 5 nm thick polymerized phospholipid membranes into which size selective pores are introduced. The porous membranes are analogous to dialysis membranes and are highly permeable to small molecules irrespective of charge but retain/exclude large molecular weight species. This architecture will allow novel enzymatic and fluorescent reporter chemistries to be used for intracellular measurements of heretofore undetectable analytes. We will optimize the formation of porous membranes via investigation of novel polymer stabilization schemes, devise strategies to deliver bioavailable sensors into the cell and utilize sensors designed for pyruvate, ATP, K+, glucose and inositol hexakisphosphate, key -cell signals whose roles are less defined in the -cell, to investigate metabolic signaling dynamics in these two important cell types. Onc fully-developed, porous lipid architectures may prove valuable for a host of other applications including large molecule drug delivery, etc.

 描述（由适用提供）：糖尿病的发生率在美国已经达到了流行病，并将在可预见的未来在所有年龄段和种族中迅速增加。通过医疗保健，工资损失等给社会带来的成本令人震惊，生活质量的改善是可以令人难以置信的。 2型糖尿病是两类的主要表现，胰岛素分泌不足和胰岛素抵抗增强。在非糖尿病药中，增加的血清葡萄糖刺激胰腺细胞的胰岛素分泌，并减少胰腺胰岛细胞的胰高血糖素分泌。葡萄糖刺激的胰岛素分泌是一个复杂的过程，通过细胞内的复杂信号通路进行调节。细胞信号传导的动力学和相应的胰岛素释放对于血清葡萄糖的正常调节至关重要，但是由于灵敏度技术的死亡，无法检测许多细胞信号。最近的研究“重新发现”了细胞在控制血清葡萄糖方面的重要性，但是对于细胞中代谢信号的动力学，了解得更少。更好地理解这些细胞类型中的细胞内信号传导和相应的调节释放对于阐明秘密异常的根本原因以及在糖尿病发作和进展中的相应作用至关重要。该提案的主要重点是开发合适的能力来监测-和细胞中的代谢和碳水化合物衍生的信号，并促进鉴定可能导致糖尿病的关键分子差异。我们将开发，表征和利用具有高度稳定的多孔磷脂结构，具有增强的质量传输能力，可检测缺乏固有的光学或电化学活性的细胞内调节剂。用大约制备磷脂支架。 5 nm厚的聚合磷脂膜引入了大小选择性孔。多孔膜类似于透析膜，并且与小分子高度渗透，无论电荷如何，但保留/排除了大分子量。这种结构将允许新型的酶促和荧光记者化学物质用于迄今无法检测的分析物的细胞内测量。我们将通过研究新型聚合物稳定方案来优化多孔膜的形成，制定策略以将可生物利用传感器传递到细胞中，并利用为丙酮酸设计的传感器， ATP，K+，葡萄糖和肌醇六磷酸，键细胞信号，其在细胞中的作用较少，以研究这两种重要细胞类型中的代谢信号动力学。 ONC完全发达的多孔脂质体系结构可能对包括大分子药物的其他许多应用，等等。