A Biophotonics Platform for Mechanotransduction and Metabolic Microscopy

用于机械传导和代谢显微镜的生物光子学平台

• 批准号: 10378760
• 负责人: VASAN VENUGOPALAN
• 金额: $ 30.9万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378760
• 关键词: 3-Dimensional; Animal Model; Biologic Characteristic; Biological Models; Biological Process; Biophotonics; Cardiac; Cell Culture System; Cell Culture Techniques; Cell Size; Cells; Cellular Metabolic Process; Characteristics; Code; Color; Complex; Connective Tissue; D Cells; Descriptor; Detection; Development; Disease; Environmental Impact; Evolution; Extracellular Matrix; Fluorescence; Fluorescence Microscopy; Fluorescence Resonance Energy Transfer; Generations; Genetic Transcription; Heterogeneity; Homeostasis; Hypertension; Impulsivity; Interdisciplinary Study; Investigation; Laboratories; Laser Scanning Confocal Microscopy; Lasers; Malignant Neoplasms; Measurement; Measures; Mechanics; Membrane Fluidity; Messenger RNA; Metabolic; Metabolism; Methods; Microscope; Microscopy; Modeling; Molecular; Morphology; Neoplasm Metastasis; Normal tissue morphology; Optical Methods; Optics; Osteoporosis; Pathway interactions; Pharmaceutical Preparations; Phase; Phenotype; Physiologic pulse; Physiological; Play; Population; Process; Property; Reporter; Role; Scanning; Signal Pathway; Signal Transduction; Specialist; System; Technology; Tissues; biological systems; bone; dynamical evolution; fluorescence lifetime imaging; high throughput screening; high-throughput drug screening; imaging capabilities; imaging modality; imaging probe; in vivo; instrument; irradiation; mechanical signal; mechanotransduction; microscopic imaging; multi-photon; multiplexed imaging; novel; second harmonic; shear stress; spectrograph; technology development; three dimensional cell culture; three-dimensional modeling; tissue culture; tool; trafficking; tumor; viscoelasticity; wound healing

A Biophotonics Platform for Mechanotransduction and Metabolic Microscopy (M3) Project Summary: (30 lines) Mechanotransduction has emerged as one of the main regulators of biological function. While the downstream effects of cellular mechanotransduction have been widely studied, the interplay between cellular mechanotransduction and metabolism remains relatively unexplored. This proposal represents a multi-disciplinary collaboration between specialists in mechanobiology, laser-tissue interactions, and advanced fluorescence microscopy methods to develop a unique biophotonics technology platform that enables the precise application of impulsive force to 2-D cell cultures, 3-D tissue cultures, and live animal models to dynamically measure cellular mechanosensitivity and cellular mechanosignaling and correlate these with metabolic state, membrane fluidity, messenger RNA (mRNA) expression, as well as cell/matrix composition, morphology, organization, and stiffness. This will be achieved through a unique integration pulsed laser microbeam irradiation used for cell/tissue stimulation with laser scanning confocal (LSCM), multi-photon (MPM), fluorescence lifetime imaging (FLIM) microscopy, and multi- spectral imaging modalities. We will verify and demonstrate the capabilities of this platform in a variety of 2-D cell culture and 3-D tissue culture systems of varying complexity and material composition and stiffness. The proposed technology development will enable a unique capability to measure and examine the dynamic cellular interplay of sensitivity to mechanical cues, mechanosignalling, and other biological system characteristics including cellular metabolism, mRNA expression, and extracellular matrix remodeling. The proposed technology platform has broad applications for the study of normal tissue development and disease and for high-throughput drug screening.

用于机械转导和代谢显微镜的生物光子学平台（M3） 项目摘要：（30行） 机械转导已成为生物功能的主要调节因子之一。而 细胞机械传导的下游效应已经被广泛研究， 细胞机械传导和代谢之间的关系仍然相对未被探索。这 该提案代表了机械生物学专家之间的多学科合作， 激光组织相互作用，先进的荧光显微镜方法，以开发一个独特的 生物光子学技术平台，能够将脉冲力精确应用于2D 细胞培养物、三维组织培养物和活体动物模型，以动态测量细胞 机械敏感性和细胞机械信号传导并将这些与代谢状态相关联， 膜流动性、信使RNA（mRNA）表达以及细胞/基质组成， 形态、组织和硬度。这将通过独特的整合来实现 激光扫描共聚焦脉冲激光微束辐照细胞/组织 （LSCM）、多光子（MPM）、荧光寿命成像（FLIM）显微镜和多光子显微镜。 光谱成像模式。我们将验证和演示此平台的功能， 各种复杂性和材料的二维细胞培养和三维组织培养系统 组成和硬度。拟议的技术开发将使一个独特的 测量和检查对机械敏感性的动态细胞相互作用的能力 提示、机械信号和其他生物系统特征，包括细胞 代谢、mRNA表达和细胞外基质重塑。所提出的技术 该平台对于正常组织发育和疾病的研究以及对于 高通量药物筛选。

项目成果

Single-shot interferometric measurement of cavitation bubble dynamics.

• DOI: 10.1364/ol.416923
• 发表时间: 2021-03-15
• 期刊: OPTICS LETTERS
• 影响因子: 3.6
• 作者: Wilson, Bryce G.;Fan, Zhenkun;Sreedasyam, Rahul;Botvinick, Elliot L.;Venugopalan, Vasan
• 通讯作者: Venugopalan, Vasan