Characterizing cell morphology, adhesion, and migration in 2.5 and 3D cell-derived extracellular matrices

该奖项由波士顿大学材料研究部生物材料项目授予，旨在表征正常和转化的人乳腺上皮细胞与2.5维和3维成纤维细胞衍生的细胞外基质之间的相互作用。这些3D培养系统由通过静电纺丝产生的3D聚合物支架系统支持的成纤维细胞衍生的细胞外基质组成。细胞与周围细胞外基质的相互作用是组织稳态和表型的关键调节剂，并且在失调时可引起严重疾病。因此，我们研究在天然环境中调节细胞-细胞外基质相互作用的复杂和多尺度机制至关重要。不幸的是，我们目前对细胞和周围细胞外基质的理解大多来自于在人工2D环境中培养的细胞，这些环境造成了人工几何和机械限制，无法捕捉体内复杂性。关键的细胞结构，形态和机械性能将在这些复杂的环境中进行表征。使用这些不同的培养系统，该项目旨在生成和整合关于复杂和天然环境中细胞粘附，迁移，细胞信号传导和基因表达的定量数据集。通过比较这些数据集，该项目希望获得对细胞与细胞外基质相互作用的复杂机制的新见解，并增强我们对天然环境中细胞形式和功能的理解。这项工作的更广泛的影响将包括为多个层次的研究人员提供一个新的定量工具箱，以回答体内细胞-基质相互作用中具有根本重要性的问题。 此外，该奖项将专注于教育下一代本科生和研究生以及多个机构的科学家，他们将发展技能，以创造定量，广泛，多尺度和综合了解体内和体外细胞-基质相互作用。人体细胞的形态和功能取决于它们与周围环境的化学、物理和机械相互作用。这些相互作用调节关键的细胞过程，一旦放松调节，可能会导致严重疾病，包括癌症、发育障碍和慢性伤口。因此，了解细胞与周围环境相互作用的基本基础对于了解正常的稳态以及探索有前途的治疗干预领域至关重要。该项目的目标是在体外环境中重建细胞的体内环境，以深入了解细胞的行为，形式和功能如何受到体内复杂周围环境的调节。这需要使用比传统上使用的更好地模拟天然组织的细胞培养系统。在拟议的工作中，我们将采取一种植根于细胞生物学，材料科学，组织工程和生物力学的综合方法来表征细胞和细胞衍生的细胞外基质之间的相互作用，这将提供一个强大的和定量的平台，以了解各种各样的生理相关过程。通过协调研究，教育和推广计划，该项目将使跨多个校区的下一代跨学科科学家和工程师，特别是在代表性不足的群体中，创造新颖，定量和广泛的理解细胞行为，以解决细胞工程和生物材料研究中的一些高价值挑战。

This award by the Biomaterials program in the Division of Materials Research to Boston University is to characterize the interactions between normal and transformed human mammary epithelial cells and 2.5- and 3-dimensional fibroblast-derived extracellular matrices. These 3D culture systems consist of fibroblast derived extracellular matrix supported by a 3D polymeric scaffold system produced by electrospinning. Cellular interactions with the surrounding extracellular matrix are key regulators of tissue homeostasis and phenotype and upon deregulation can cause severe diseases. Thus, it is critical that we study the complex and multi-scale mechanisms regulating cell-extracellular matrix interactions in native like environments. Unfortunately, most of our current understanding between cells and surrounding extra-cellular matrices arises from cells cultured on artificial 2D environments that pose artificial geometric and mechanical restrictions and are unable to capture the in vivo complexity. Key cellular structural, morphological and mechanical properties will be characterized in these complex environments. Using these different culture systems, the project aims to generate and integrate quantitative datasets on cell adhesion, migration, cell signaling and gene expression in complex and native like environments. By comparing these datasets, the project expects to obtain new insights into the complex mechanisms, by which cells interact with the extra cellular matrix and enhance our understanding of cellular form and function in native environments. Broader impacts of this work will include providing researchers at multiple levels with a new quantitative toolbox to answer questions of fundamental importance in cell-matrix interactions in vivo. In addition, this award will focus educating the next generation of undergraduate and graduate students and scientists at multiple institutions who will develop skills to create a quantitative, broad based, multi-scale and integrated understanding of cell-matrix interactions in both in vivo and in vitro. The form and function of cells in the human body rests on their chemical, physical and mechanical interactions with the surrounding environment. These interactions regulate key cellular processes and upon deregulation can cause severe diseases, including cancer, developmental disorders and chronic wounds. Understanding the fundamental basis of cellular interactions with the surrounding environment is therefore of critical importance for gaining insights into the normal homeostasis as well as to probe promising areas of therapeutic interventions. The goals of this project are to recreate the in vivo environment of cells in an in vitro setting to gain insights into how cellular behavior, form and function are regulated by the complex surrounding environment in vivo. This requires the use of cell culture systems that better mimic native tissues than what has been used traditionally. In the proposed work, we will undertake an integrated approach rooted in cell biology, material science, tissue engineering and biomechanics to characterize the interactions between cells and cell-derived extracellular matrices that will provide a robust and quantitative platform to understand a wide variety of physiologically relevant processes. Using a coordinated research, education and outreach plan, this project will enable the next generation of interdisciplinary scientists and engineers across multiple campuses, and particularly among under-represented groups, to create novel, quantitative and a broad based understanding of cellular behavior to address a number of high-value challenges in cellular engineering and biomaterials research.