The Contribution of Biomechanics of Cells and Extracellular Matrix to Cancer Invasion

该项目的目的是开发一个微流体系统来研究细胞力学性能与迁移之间的关系。在项目的初始阶段，将使用原子力显微镜评估单细胞（恶性和非相同表型）的机械特性。这将在单细胞水平上提供关于不同种群的基本数据集。此外，文献中有许多例子表明，晚期癌细胞产生大量的细胞外基质蛋白，这有助于肿瘤的整体刚性。因此，与早期肿瘤相似的细胞聚集体的机械特性将被评估。为此，将对细胞进行三维培养，形成组织样菌落。随着对单个细胞和肿瘤样细胞聚集体在静态条件下的力学行为的了解，将开发微流体装置来评估细胞力学特性与细胞迁移之间的关系。该装置将被设计用于创造仿生物理屏障和生理流体条件，如趋化梯度。计算软件，例如Comsol将用于识别理想的几何形状来实现这一目标。然后在芯片上评估细胞力学特性和所选候选药物对细胞迁移的影响。

The aim of the project is to develop a microfluidic system to study the correlation between cell mechanical properties and migration. At the initial stage of the project, mechanical properties of single cells (malignant and not of the same phenotype) will be evaluated using atomic force microscopy. This will provide a basic data set about different populations at the single-cell level. Furthermore, there are many examples in the literature showing that cancer cells at advanced stages produce substantially higher amounts of extracellular matrix proteins that contribute to the overall rigidity of a tumor. Therefore, mechanical properties of cell aggregates with dimensions resembling those of an early stage tumor will be evaluated. To do this, 3D culture of cells will be conducted to form tissue-like colonies. With the knowledge of the mechanical behavior of single cells and of tumor-like cell aggregates in static conditions, microfluidic devices will be developed to evaluate the relation between cell mechanical properties and cell migration. The device will be designed to create biomimetic physical barriers and physiological fluidic conditions such as chemotactic gradients. Computational software, for example Comsol will be used to identify desirable geometries to achieve this. The effect of cell mechanical properties and chosen drug candidates on cell migration will then be evaluated on chip.