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The Role of Coherent Rotation in Adult Tissue Remodeling

相干旋转在成人组织重塑中的作用

基本信息

批准号：
10926212
负责人：
Kandice Tanner
金额：
$ 74.18万
依托单位：
DIVISION OF BASIC SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10926212
关键词：
Address Adult Architecture Atomic Force Microscopy Biochemical Biological Biomimetics Biophysics Brain Breast Cells Complex Cues Distant Metastasis Ecology Environment Exhibits Extracellular Matrix Glioblastoma Habitats Heterogeneity Hydrogels Intervention Ligands Lung Maintenance Malignant Neoplasms Measures Mechanics Microscope Modeling Morbidity - disease rate Neoplasm Metastasis Noise Normal Cell Normal tissue morphology Organ Patients Phenotype Physiological Primary Neoplasm Research Resolution Rheology Role Rotation Secondary Lesion Signal Transduction System Techniques Testing Tissues Tumor Promotion Tumor Suppression Zebrafish design experience extracellular human model in vivo insight mechanical properties mechanical signal meter mortality neoplastic cell optic trap optical traps physical property response three dimensional cell culture tool tumor tumor progression viscoelasticity

项目摘要

Metastasis remains the primary cause of patient morbidity and mortality. The reality is that we are not detecting secondary lesions at an early enough stage to make meaningful intervention. There is a burgeoning field investigating the role of tissue mechanics and architecture in normal tissue maintenance and in cancer promotion. However, the field is still struggling to decouple the physical from the better-known biochemical determinants of cell fate. Simply put, how do the physical properties of the tissue environment influence the emergence of tumor promotion or tumor suppression? The bulk of our current understanding is derived from characterization of mechanical properties of tissues, cells, and ECM hydrogels using bulk rheological or nm scale techniques such as Atomic force microscopy (AFM).The Tanner lab developed new 3D culture models, incorporating architectural complexity with well-defined extracellular matrix ligand availability to mimic physiological tissue. In addition, we developed tools that directly quantitate the physical cues that a cell will see in vivo within native tissue, and in the presence of physiologic noise, to finally address these questions. To achieve this in vivo characterization, the Tanner lab designed and built a microscope that employed active microrheology optical trapping in vivo, which allowed for the quantitation of mechanical heterogeneities with micrometer spatial resolution in living zebrafish.

转移仍然是患者发病和死亡的主要原因。现实情况是，我们没有在足够早的阶段检测到继发性病变，无法进行有意义的干预。有一个新兴的领域调查的作用，组织力学和建筑在正常组织的维护和癌症的促进。然而，该领域仍在努力将细胞命运的物理决定因素与更知名的生物化学决定因素脱钩。简单地说，组织环境的物理性质如何影响肿瘤促进或肿瘤抑制的出现？我们目前的大部分理解来自于使用本体流变学或纳米尺度技术（如原子力显微镜（AFM））表征组织、细胞和ECM水凝胶的机械特性。坦纳实验室开发了新的3D培养模型，将结构复杂性与定义明确的细胞外基质配体可用性结合起来，以模拟生理组织。此外，我们开发了直接定量细胞在体内天然组织中以及在生理噪声存在下看到的物理线索的工具，以最终解决这些问题。为了实现这种体内表征，坦纳实验室设计并建造了一种显微镜，该显微镜在体内采用主动显微流变学光学捕获，从而可以在活体斑马鱼中以微米空间分辨率定量机械不均匀性。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

In situ calibration of position detection in an optical trap for active microrheology in viscous materials.

对粘性材料中的主动微流变学光阱中的位置检测进行原位校准。

DOI：
10.1364/oe.25.001746
发表时间：
2017
期刊：
Optics express
影响因子：
3.8
作者：
Staunton,JackR;Blehm,Ben;Devine,Alexus;Tanner,Kandice
通讯作者：
Tanner,Kandice

Patterned collagen fibers orient branching mammary epithelium through distinct signaling modules.

DOI：
10.1016/j.cub.2013.03.032
发表时间：
2013-04-22
期刊：
CURRENT BIOLOGY
影响因子：
9.2
作者：
Brownfield, Douglas G.;Venugopalan, Gautham;Lo, Alvin;Mori, Hidetoshi;Tanner, Kandice;Fletcher, Daniel A.;Bissell, Mina J.
通讯作者：
Bissell, Mina J.

Probing cellular response to topography in three dimensions.

DOI：
10.1016/j.biomaterials.2019.01.009
发表时间：
2019-01
期刊：
Biomaterials
影响因子：
14
作者：
C. Paul;Alex M. Hruska;J. Staunton;Hannah A. Burr;K. Daly;Jiyun Kim;N. Jiang;K. Tanner
通讯作者：
C. Paul;Alex M. Hruska;J. Staunton;Hannah A. Burr;K. Daly;Jiyun Kim;N. Jiang;K. Tanner

Regulation of the basement membrane by epithelia generated forces.