Nanostructured Matrices for Cancer Cell Biology

项目总结（见说明）： 癌症生物学中的一个广泛挑战是开发在生理学上与癌症相关的细胞培养模型。 相关的是，常驻细胞显示出疾病背后的复杂行为。此外，为细胞提供均匀和一致的微环境的细胞培养模型将减少通常观察到的细胞行为的分布，因此将导致可用于定量比较不同细胞群体的行为的稳健测定。拟议的工作是为了改善使用的平面文化进行的塑料盘，往往是不够的，以捕捉相关的细胞行为，和常见的Matrigel三维矩阵，一直是重要的癌症生物学，尽管可变的属性和不完全定义的组成，这种天然基质。拟议的项目将采用分子方法开发两类定义的基质。一种是基于纳米图案基底，这是很重要的，因为这种图案可以用来限制粘着斑的大小，使它们与组织内细胞中观察到的情况更相关， 排列成轨道图案为细胞提供了可再现的路径，使其沿着迁移，从而消除了异质行为的大的来源。第二种方法是基于从肽和肽两亲物自组装的三维基质，并且对于使用完全限定的组合物是重要的，所述组合物还允许在掺入肽和蛋白质基序中具有广泛的灵活性。这两种设计都强调在纳米尺度上对材料性质的控制，无论是在图案化的细胞外基质的尺寸上还是在三维基质中的原纤维的尺寸上，从而模仿蛋白质基质的物理特征。该项目强调基质的开发和表征，但也包括具有脑癌和胰腺癌生物学和医学专业知识的研究人员，为评估基质提供真实的试验平台。该项目的主要目标是开发培养系统，为细胞提供一个支持复杂生物功能的微环境，并实现对细胞功能的强大定量分析。这项工作，如果成功的话，将因此在基础研究实验室中是重要的，而且在高通量筛选中使用基于细胞的测定的程序中也是重要的，并且可能作为在治疗肿瘤中提供组织再生的材料。 癌

PROJECT SUMMARY (See instructions): A broad challenge in cancer biology is the development of cell culture models that are physiologically relevant in that the resident cells display the complex behaviors that underiie disease. Further, cell culture models that provide a uniform and consistent microenvironment to the cells will decrease the distribution of cellular behaviors that are typically observed and therefore will lead to robust assays that can be used to quantitatively compare the behaviors of different cell populations. The proposed work is intended to improve on the use of planar cultures performed on plastic dishes that are often insufficient to capture relevant cell behaviors, and the common Matrigel three-dimensional matrix that has been important to cancer biology, notwithstanding the variable properties of and incompletely defined composition of this natural matrix. The proposed project will pursue molecular approaches to developing two classes of defined matrices. One is based on nanopatterned substrates and is significant because the patterns can be used to constrain the sizes of focal adhesionsmaking them more relevant to what is observed in cells within tissueand when arranged into track patterns provides a reproducible path for cells to migrate along, removing a large source of heterogeneous behavior. The second approach is based on three-dimensional matrices that are selfassembled from peptides and peptide amphiphiles and is significant for the use of a completely defined composition that also permits wide flexibility in incorporating peptide and protein motifs. Both designs emphasize the control of material properties at the nanoscaleeither in the dimensions of patterned extracellular matrix or the sizes of the fibrils in the three dimensional matricesand therefore mimic the physical features of protein matrix. The project emphasizes the development and characterization of the matrices, but also includes investigators with expertise in the biology and medicine of brain and pancreafic cancer, providing a real test-bed for evaluating the matrices. The broad goal of the project is to develop culture systems that are unmatched for providing cells with a microenvironment that supports complex biological functions and that enable robust, quantitative assays of cell function. This work, if successful, will therefore be important in basic research laboratories but also in programs to use cell-based assays in high throughput screens and possibly as materials that provide for regeneration of tissue in the treatment of cancer.