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CAREER: Decoding the Mechanical Control of Tissue Growth

职业：解码组织生长的机械控制

基本信息

批准号：
1652910
负责人：
Otger Campas
金额：
$ 50万
依托单位：
University of California-Santa Barbara
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2023-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1652910&HistoricalAwards=false
关键词：
CAREER Decoding Mechanical Control Tissue

项目摘要

In order to build healthy tissues and organs, cells need constant biochemical and mechanical feedback from their environment. Several diseases, including tumor growth, are linked to abnormal tissue hardening or softening, a mechanical effect known to either cause or exacerbate the progression of the disease. However, it remains largely unknown how these mechanical effects control tissue growth and the appearance of disease, simply because no methodologies existed to reveal how cells respond to these mechanical cues. The research supported by this Faculty Early Career Development (CAREER) award will overcome these difficulties by using a set of cutting-edge techniques to reveal for the first time the mechanical environment of cells and their response to this environment directly as tissues are being built. Beyond the discovery of new fundamental mechanisms underlying tissue and organ growth, the results of this research will contribute to society by helping in many tissue engineering applications as well as in the understanding and diagnosis of cancer and several other diseases associated with tissue mechanical abnormalities. Moreover, this project will provide many opportunities for underrepresented students to engage in interdisciplinary research projects, thereby promoting engineering education.Mechanical cues, such as forces or the mechanical properties of the cellular microenvironment, are known to affect the behavior of cells in culture conditions, but it is unknown how these affect cells in living 3D tissues. A key necessary step to approach biomechanics and mechanobiology questions in 3D multicellular systems, especially during the formation of tissues and organs, is being able to quantitatively measure the endogenous mechanical cues in these systems. Using two novel microdroplet-based techniques that enable a direct quantification of spatiotemporal variations in mechanical forces and mechanical properties within developing 3D tissues, the proposed research will reveal the differential mechanical cues that cells perceive during vertebrate body axis elongation, decode the spatial and temporal characteristics of such mechanical cues, and quantify the mechanical response of cells to controlled mechanical stimuli, all within the developing zebrafish embryo.

为了构建健康的组织和器官，细胞需要来自其环境的持续生化和机械反馈。包括肿瘤生长在内的几种疾病都与异常的组织硬化或软化有关，这是一种已知会导致或加剧疾病进展的机械效应。然而，这些机械效应如何控制组织生长和疾病的出现在很大程度上仍然是未知的，这仅仅是因为没有方法来揭示细胞如何对这些机械信号做出反应。由该学院早期职业发展（CAREER）奖支持的研究将通过使用一套尖端技术来克服这些困难，以首次揭示细胞的机械环境及其在组织构建时对这种环境的直接反应。除了发现组织和器官生长的新的基本机制之外，这项研究的结果还将有助于许多组织工程应用以及癌症和与组织机械异常相关的其他几种疾病的理解和诊断。此外，该项目还将为代表性不足的学生提供许多从事跨学科研究项目的机会，从而促进工程教育。机械线索，如力或细胞微环境的机械特性，已知会影响培养条件下的细胞行为，但尚不清楚这些如何影响活的三维组织中的细胞。在3D多细胞系统中，特别是在组织和器官的形成过程中，解决生物力学和机械生物学问题的关键步骤是能够定量测量这些系统中的内源性机械线索。使用两种新的基于微滴的技术，能够直接量化发育中3D组织内机械力和机械特性的时空变化，拟议的研究将揭示细胞在脊椎动物体轴伸长期间感知的差异机械线索，解码这种机械线索的空间和时间特征，并量化细胞对受控机械刺激的机械反应，都在发育中的斑马鱼胚胎中。