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.

机械转导和代谢显微镜（M3）的生物光音阶平台（M3） 项目摘要：（ 30行） 机械转导已成为生物功能的主要调节剂之一。尽管 细胞机械转导的下游效应已被广泛研究，相互作用 在细胞机械转导和代谢之间仍然相对尚未探索。这 提案代表了机械生物学专家之间的多学科合作， 激光 - 组织相互作用和晚期荧光显微镜方法开发独特的 生物探测技术平台，可以将冲动力精确地应用于2-D 细胞培养物，3-D组织培养物和活动物模型，以动态测量细胞 机械敏感和细胞机械信号，并将它们与代谢状态相关联， 膜流动性，信使RNA（mRNA）表达以及细胞/基质组成， 形态，组织和僵硬。这将通过独特的整合来实现 用激光扫描共聚焦用于细胞/组织刺激的脉冲激光微膜照射 （LSCM），多光子（MPM），荧光寿命成像（FLIM）显微镜和多个 光谱成像方式。我们将在 各种二维细胞培养和3-D组织培养系统的复杂性和材料的变化 组成和刚度。拟议的技术开发将使独特 测量和检查机械灵敏度的动态细胞相互作用的能力 提示，机械签名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。提出的技术 平台在研究正常组织发育和疾病以及 高通量药物筛查。

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