Lightsheet Microscope

了解生物系统功能的机械原理是现代研究的一个关键目标。细胞和组织力学的重要性是基本的动态过程发生在发展和组织形成的定量描述，但也在癌症。我们使用光片显微镜研究了细胞的集体和个体迁移模式，这允许生成快速的组织，生物体和癌症球体的3D体积，这些体积代表了肿瘤的模型系统。通过标记细胞核，我们跟踪组织的所有单个细胞，从而能够量化组织流场和迁移特性。使用嵌入组织中的弹性水凝胶珠，我们还能够确定组织中的机械张力。通过使用主动流体的方法，这使我们能够了解到，在何种程度上的全球动态运动是由被动的物理相互作用，以及在主动力的产生是需要一个一致的描述。然后将通过使用光消融的局部损伤或通过使用光遗传学触发组织的局部收缩来干扰系统来检查所得到的定量模型。目前，还没有探索3D细胞跟踪与基于光片的光操纵的组合，我们的目标是用本申请中详细描述的项目来填补这一空白。

Understanding the mechanical principles governing the function of biological systems is a key goal of modern research. The importance of cell and tissue mechanics is fundamental for a quantitative description of the dynamical processes occurring during development and tissue formation but also in cancer. We study the collective and individual migration patterns of cells using light sheet microscopy, that allows to generate rapid 3D volumes of tissue, organisms and cancer spheroids which represent a model system for tumors. By marking the cell nuclei, we track all individual cells of a tissue, and are thus able to quantify the tissue flow fields and migration characteristics. Using elastic hydrogel beads embedded in the tissue we are furthermore able to determine the mechanical tension in the tissue. By using an active fluid approach this enables us to understand to which extend the global dynamical motion is driven by passive physical interactions, and where active force generation is required for a consistent description. The resulting quantitative models will then be checked by interfering with the systems using either local damage by photoablation or by triggering local contraction of the tissue using optogenetics. Currently, the combination of 3D cell tracking with light sheet based photomanipulation is not explored, and we aim to fill this gap with the projects detailed in this application.