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

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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.