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Robust microdroplet-based mechanical probes for wide-ranging mechanobiology applications

坚固的基于微滴的机械探针，适用于广泛的机械生物学应用

基本信息

批准号：
10021683
负责人：
Otger Campas
金额：
$ 43.48万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-20 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10021683
关键词：
3-Dimensional Adult Affect Architecture Benchmarking Biochemical Biological Biological Models Cell Communication Cell Culture Techniques Cell Surface Receptors Cells Cellular Spheroids Chemicals Chemistry Communities Cues Custom Defect Development Disease Disease Progression Embryo Embryonic Development Ensure Environment Fibrosis Fluorocarbons Goals Grant Homeostasis Image Impairment In Situ In Vitro Knowledge Label Magnetic nanoparticles Magnetism Maintenance Malignant Neoplasms Measurement Measures Mechanical Stress Mechanics Methodology Methods Oils Organ Organoids Outcome Oxides Performance Physiological Play Positioning Attribute Process Property Receptor Cell Reporting Reproducibility Role Signal Transduction Solubility Stress Surface System Techniques Technology Testing Time Tissues Transducers Visualization Work base behavior in vitro biological systems cell behavior commercialization cyanine dye ferrite ferrofluid fluorophore in vivo innovation interfacial magnetic field malignant phenotype mechanical force nanoparticle new technology novel organ growth prevent sensor stem cell differentiation surfactant technology development three dimensional cell culture tool tumor tumor progression

项目摘要

PROJECT SUMMARY Mechanical cues critically affect cell behaviors that are central to embryonic development, organ formation and the maintenance of tissue architecture and homeostasis. Both mechanical forces and the material properties of the cellular microenvironment (e.g., stiffness) are known to direct stem cell differentiation as well as alter the progression of malignant phenotypes during tumor progression. While it is generally acknowledged that mechanical forces and the material properties of the cellular microenvironment play a key role in the control of cell behaviors in vitro, the lack of technologies to perform quantitative measurements of mechanics in 3D cellular microenvironments has considerably hindered our ability to understand the role of mechanics in more physiologically relevant environments. PI Campas and coworkers have recently reported a novel methodology that enables direct in vivo and in situ mechanical measurements within 3D cellular microenvironments, including living tissues, for the first time. While groundbreaking, these methods, which make use of fluorescently-labeled, magnetically-responsive microdroplets of perfluorinated oil as mechanical sensors and actuators, remain strongly limited in scope because of current chemistry used to prepare the microdroplets. The current finicky chemical composition of the microdroplets strongly limits the scope of the technique, hampers the reproducibility of the measurements and precludes the dissemination of these methods to the wide biological and biomedical communities. In this multi-PI technology development grant, Campas, Sletten, and Zink team up to solve the existing problems with the microdroplet technology by developing new robust chemistries, including fluorinated surfactants, fluorophores, and magnetic nanoparticles, to enable accurate mechanical measurements with microdroplets in a wide range of biological systems, from living tissues and organs to organoids, tumors and 3D cell culture. In Aim 1, we will develop surfactants and fluorophores to properly control the droplet’s interfacial tension, the cell droplet interactions and their visualization in 3D multicellular systems. In Aim 2, we will develop robust perfluorocarbon-based ferrofluids with controlled interfacial tension, cell-droplet interactions and with strong magnetic properties enabling the application of larger forces. In Aim 3, we will test the functionality of the newly synthesized compounds and assess their performance in mechanical measurements in well-established 3D multicellular systems, both in vitro and in vivo. Upon completion of these aims, we will achieve an optimized microdroplet technology that is ready for commercialization and can be used in a wide range of systems, including living tissues, organoids, embryoid bodies, tumors and 3D cell culture, thereby making accessible these new tools for the study of mechanical cues (mechanobiology) in vivo to the entire biological and biomedical communities and potentially transforming our understanding of biological systems.

项目总结