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SingleCellECM: Dynamically controllable 3D niches to study cell-ECM interactions on a single cell level
Cells reside within an extracellular matrix (ECM), which is composed of many proteins and biomolecules, and instruct cell function through many biophysical and biochemical signals. SingleCellECM is a novel cell encapsulation platform that open new opportunities in study of cell-ECM interactions.
Mammalian cells reside within an extracellular matrix (ECM), which is composed of many proteins and other biomolecules, and instruct cell function through many biophysical and biochemical signals. Research on cell-ECM interactions is a fundamental topic in the fields of cell biology, tissue engineering, and biomaterials. Toward this end, engineered cell culture platforms have been designed based on natural ECM protein mixtures and synthetic hydrogels. [1] A current approach to study cell-ECM interactions involves 3D encapsulation in a material that closely resembles the natural extracellular environment. Mechanical and biochemical properties of this material are manipulated to study their effects on cell functions. These materials still lack some key properties that are needed to effectively study dynamic cell-ECM interactions. The conventional encapsulation platforms are not able to provide spatiotemporal control over the mechanical properties of the cell microenvironment and over the presentation of biochemical ligands. Moreover, they lack control over the geometry of the 3D cell niche. In addition, the cells that are encapsulated in bulk hydrogels are exposed to heterogeneous stimuli. This results in averaged cell response making it difficult to decouple the effects of the different signals on cell development. In this project a novel cell encapsulation platform is being developed that will provide high degree of control over the biophysical and biochemical properties of single cell microenvironments in space and time. [2] The SingleCellECM is a multi-disciplinary research project consisting of different tasks including microfabrication of the patterned gel surfaces; development and chemical synthesis of dynamic chemistries for stimuli-responsive hydrogel platforms; developing of microscale patterns and 3D photopatterning; and biological evaluation to study cell-material interactions.
We search motivated students with different backgrounds to contribute to the project.
Mammalian cells reside within an extracellular matrix (ECM), which is composed of many proteins and other biomolecules, and instruct cell function through many biophysical and biochemical signals. Research on cell-ECM interactions is a fundamental topic in the fields of cell biology, tissue engineering, and biomaterials. Toward this end, engineered cell culture platforms have been designed based on natural ECM protein mixtures and synthetic hydrogels. [1] A current approach to study cell-ECM interactions involves 3D encapsulation in a material that closely resembles the natural extracellular environment. Mechanical and biochemical properties of this material are manipulated to study their effects on cell functions. These materials still lack some key properties that are needed to effectively study dynamic cell-ECM interactions. The conventional encapsulation platforms are not able to provide spatiotemporal control over the mechanical properties of the cell microenvironment and over the presentation of biochemical ligands. Moreover, they lack control over the geometry of the 3D cell niche. In addition, the cells that are encapsulated in bulk hydrogels are exposed to heterogeneous stimuli. This results in averaged cell response making it difficult to decouple the effects of the different signals on cell development. In this project a novel cell encapsulation platform is being developed that will provide high degree of control over the biophysical and biochemical properties of single cell microenvironments in space and time. [2] The SingleCellECM is a multi-disciplinary research project consisting of different tasks including microfabrication of the patterned gel surfaces; development and chemical synthesis of dynamic chemistries for stimuli-responsive hydrogel platforms; developing of microscale patterns and 3D photopatterning; and biological evaluation to study cell-material interactions.
We search motivated students with different backgrounds to contribute to the project.
**• Device manufacturing through microfabrication**
The primary goal of this project is to design series of photomasks with micropatterns of different sizes and shapes. Consequently, the utilization of these masks in photolithography process to yield patterned silicon substrates and the application patterns on bioactive hydrogel matrices via hydrogel molding. Further aims include the characterization of fabricated surfaces and optimization of photolithography and molding conditions.
**• Biological evaluation**
The SingleCellECM is going to be employed to study cell-material interactions on a single cell level. Cells will be encapsulated in 3D and the cell behavior in response to the cues provided by the niche will be tested. The influence of different parameters will be examined including shape, stiffness and biologically activity of the niche. Using the utility of SingleCellECM and dynamic photoresponsive properties of the hydrogel, the cues will be presented to the cells in different combinations, with different gradients and in a controlled spatiotemporal manner.
**• Automated analysis**
The biological evaluation using SingleCellECM is an efficient process rapidly accumulating numerous cell images of that require a comprehensive analysis. To make the analysis as efficient as the testing this process has to be automated. Here, the code has to be designed that will ease the analysis of thousands of singly encapsulated cell executing single cell recognition and counting.
**• Device manufacturing through microfabrication** The primary goal of this project is to design series of photomasks with micropatterns of different sizes and shapes. Consequently, the utilization of these masks in photolithography process to yield patterned silicon substrates and the application patterns on bioactive hydrogel matrices via hydrogel molding. Further aims include the characterization of fabricated surfaces and optimization of photolithography and molding conditions. **• Biological evaluation** The SingleCellECM is going to be employed to study cell-material interactions on a single cell level. Cells will be encapsulated in 3D and the cell behavior in response to the cues provided by the niche will be tested. The influence of different parameters will be examined including shape, stiffness and biologically activity of the niche. Using the utility of SingleCellECM and dynamic photoresponsive properties of the hydrogel, the cues will be presented to the cells in different combinations, with different gradients and in a controlled spatiotemporal manner. **• Automated analysis** The biological evaluation using SingleCellECM is an efficient process rapidly accumulating numerous cell images of that require a comprehensive analysis. To make the analysis as efficient as the testing this process has to be automated. Here, the code has to be designed that will ease the analysis of thousands of singly encapsulated cell executing single cell recognition and counting.