Lightsheet Microscope

理解支配生物系统功能的力学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对于定量描述在发育和组织形成过程中发生的动态过程是基本的，在癌症中也是如此。我们使用光片显微镜研究细胞的集体和个人迁移模式，这使得能够快速生成代表肿瘤模型系统的组织、生物体和癌症球体的3D体积。通过标记细胞核，我们跟踪组织的所有单个细胞，从而能够量化组织的流场和迁移特征。利用嵌入在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。通过使用主动流体方法，这使我们能够了解全球动力运动在何种程度上是由被动物理相互作用驱动的，以及需要在哪里产生主动力才能得到一致的描述。然后，将通过使用光消融的局部损伤或通过利用光遗传学触发组织的局部收缩来干扰系统来检查所产生的定量模型。目前，还没有探索将3D细胞跟踪与基于光片的光操纵相结合，我们的目标是通过本申请中详细介绍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.