Kim:Research: Difference between revisions
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'''1. Engineering biomimetic in vitro cell culture models for tissue engineering and cell biological applications''' <br> | '''1. Engineering biomimetic in vitro cell culture models for tissue engineering and cell biological applications''' <br> | ||
Our curent research focuses on engineering combinatorial cellular microenvironment through use of variable nano-patterns, and soluble and matrix-bound cell guidance cues in a single experiment, which better mimics the in vivo microenvironment under physiological conditions. For example, we are developing a microfluidics-based on chip assay integrated with complex nanoscale topographic features to enable the analysis of concerted cell responses to composite gradients of precisely generated and aligned surface-bound ECM molecules and diffusible guidance cues or topographic guidance cues. Using these tools, we strive to systematically characterize live cells to wide spectra of dynamically changing combination of mechanical and chemical stimuli (e.g. ECM proteins, topographic, growth factors and signal transduction pathway inhibitors). The proposed measurements are highly resolved in time and space, using a variety of live cell probes and highly defined extracellular conditions. In collaboration with other nanofabrication groups, we are developing nanotopography-integrated cell culture systems and biomaterial tissue scaffolds using UV-assisted capillary force lithography and/or nanoimprinting techniques. For high-throughput analysis, we are also working to combine a large area nanopatterned substrate with a traditional multi-well tissue culture plate. We aim to use these tools to gain new mechanistic insights into cell signaling and function, to design new therapies or diagnostic tests for cancer progression and cardiovascular diseases, and to establish organizing principles for development of precisely defined scaffolds for advanced tissue engineering applications. <br> <br> | Our curent research focuses on engineering combinatorial cellular microenvironment through use of variable nano-patterns, and soluble and matrix-bound cell guidance cues in a single experiment, which better mimics the in vivo microenvironment under physiological conditions. For example, we are developing a microfluidics-based on chip assay integrated with complex nanoscale topographic features to enable the analysis of concerted cell responses to composite gradients of precisely generated and aligned surface-bound ECM molecules and diffusible guidance cues or topographic guidance cues. Using these tools, we strive to systematically characterize live cells to wide spectra of dynamically changing combination of mechanical and chemical stimuli (e.g. ECM proteins, topographic, growth factors and signal transduction pathway inhibitors). The proposed measurements are highly resolved in time and space, using a variety of live cell probes and highly defined extracellular conditions. In collaboration with other nanofabrication groups, we are developing nanotopography-integrated cell culture systems and biomaterial tissue scaffolds using UV-assisted capillary force lithography and/or nanoimprinting techniques. For high-throughput analysis, we are also working to combine a large area nanopatterned substrate with a traditional multi-well tissue culture plate. We aim to use these tools to gain new mechanistic insights into cell signaling and function, to design new therapies or diagnostic tests for cancer progression and cardiovascular diseases, and to establish organizing principles for development of precisely defined scaffolds for advanced tissue engineering applications. <br> <br> | ||
'''2. Systems mechanobiology of cell-cell and cell-matrix interactions in collective cell migration''' <br> | '''2. Systems mechanobiology of cell-cell and cell-matrix interactions in collective cell migration''' <br> | ||
Mechanotransduction - from how cells sense mechanical forces in different tissues to how these mechanical forces are transduced into biochemical signals - is an essential biological process in development, normal physiology and disease. In this exciting area, we are particularly interested in investigate the role of mechano-biological processes associated with cell-cell and cell-matrix adhesions (e.g. topography and rigidity of the extracellular matrix) in the regulation of collective cell migration. Using a combination of various techniques, from molecular biology to nanotechnology and live cell imaging, for example, we have been accumulating interesting data suggesting that one of the most important factors distinguishing metastatic from non-metastatic cells could be their ability to collectively invade and migrate towards blood vessels by physically interacting with the surrounding extracellular matrices. By experimenting with the nanofabricated cell adhesion substratum (i.e. quasi 3D cell culture system) and 3D natural/synthetic extracellular matrices, we are also investigating the biophysical and signaling mechanisms of collective cell migration driven by the hypothesis that the physical interaction of migrating cells with the surrounding ECM has a crucial role in the collective guidance of cell migration in the context of cancer invasion and wound healing. To test this hypothesis, we recently developed a micro/nanofabricated collective migration assay as an enabling tool for analysis and control of cancer cell invasion and epithelial/endothelial wound healing in a high-throughput, controlled manner. Using these tools, we explore the potential role of mechanical guidance in the regulation of collective cell migration under the presence/absence of growth factor-induced signals, and test their biomedical implication by screening cytoskeletal and signal transduction pathways. <br> <br> | Mechanotransduction - from how cells sense mechanical forces in different tissues to how these mechanical forces are transduced into biochemical signals - is an essential biological process in development, normal physiology and disease. In this exciting area, we are particularly interested in investigate the role of mechano-biological processes associated with cell-cell and cell-matrix adhesions (e.g. topography and rigidity of the extracellular matrix) in the regulation of collective cell migration. Using a combination of various techniques, from molecular biology to nanotechnology and live cell imaging, for example, we have been accumulating interesting data suggesting that one of the most important factors distinguishing metastatic from non-metastatic cells could be their ability to collectively invade and migrate towards blood vessels by physically interacting with the surrounding extracellular matrices. By experimenting with the nanofabricated cell adhesion substratum (i.e. quasi 3D cell culture system) and 3D natural/synthetic extracellular matrices, we are also investigating the biophysical and signaling mechanisms of collective cell migration driven by the hypothesis that the physical interaction of migrating cells with the surrounding ECM has a crucial role in the collective guidance of cell migration in the context of cancer invasion and wound healing. To test this hypothesis, we recently developed a micro/nanofabricated collective migration assay as an enabling tool for analysis and control of cancer cell invasion and epithelial/endothelial wound healing in a high-throughput, controlled manner. Using these tools, we explore the potential role of mechanical guidance in the regulation of collective cell migration under the presence/absence of growth factor-induced signals, and test their biomedical implication by screening cytoskeletal and signal transduction pathways. <br> <br> |
Revision as of 13:09, 17 September 2010
Our research focuses on investigating how the engineered microenvironments direct cell function and tissue regeneration. In particular, we are exploring extracellular matrix (topology, rigidity, dimensionality, etc) regulation of cell fate and function in developmental, physiological and pathological process. Several specific thrusts of the current research program include: microengineered platforms for cell-matrix mechanobiology, mechanical regulation of cancer cell invasion and collective cell migration, microscale cardiovascular tissue engineering, and BioMEMS for stem/progenitor cell niche engineering. Here is a summary of our current research projects.
1. Engineering biomimetic in vitro cell culture models for tissue engineering and cell biological applications 2. Systems mechanobiology of cell-cell and cell-matrix interactions in collective cell migration 3. Multiscale fabrication approaches to stem cell niche engineering and cardiovascular tissue engineering |