The Role of Coherent Rotation in Adult Tissue Remodeling

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发现继发性病变，从而无法进行有意义的干预。有一个新兴的领域研究组织力学和结构在正常组织维护和癌症促进中的作用。然而，该领域仍在努力将物理因素与众所周知的细胞命运的生化决定因素分离开来。简单地说，组织环境的物理性质是如何影响肿瘤促进或肿瘤抑制的出现的？我们目前的大部分理解来自于组织、细胞和ECM水凝胶的力学特性表征，这些表征使用了体流变学或纳米尺度技术，如原子力显微镜（AFM）。Tanner实验室开发了新的3D培养模型，将结构复杂性与定义良好的细胞外基质配体可用性结合起来，以模拟生理组织。此外，我们还开发了一种工具，可以直接量化细胞在体内原生组织中看到的物理信号，以及存在生理噪声的情况，最终解决这些问题。为了实现这种体内表征，Tanner实验室设计并建造了一种采用主动微流变光学捕获的显微镜，可以在活体斑马鱼中以微米级的空间分辨率定量测量机械异质性。

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.