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Engineering of Biomaterials and Cellular Microenvironments, Cell-Environment Interactions, Biomolecular Engineering
Research Interests: Engineering of cellular microenvironments to regulate cell behavior and fate Cell fate commitment and tissue formation during animal development are guided by microenvironmental signals with great spatial and temporal precision. The success of tissue engineering relies on our ability of mimicking Mother Nature to provide precisely controlled environmental cues to guide cells to proliferate, differentiate, migrate, and assemble into functional tissues. Microenvironmental cues critical for regulating cell behavior and fate include both biochemical signals, such as soluble factors and insoluble factors associated with extracellular matrix or neighboring cells, and physical signals, such as shear stress and the elastic properties of the environment. We are building cellular microenvironments in a spatially and temporally controlled manner to direct cell behavior and fate by using interdisciplinary approaches encompassing material science, protein engineering, developmental biology, cell biology and microfabrication technologies. Molecular engineering of stimuli responsive biomaterials Biomaterials that can change their properties in response to external chemical or physical stimuli are extremely useful in biomedical applications. These smart materials can sense and respond to their environment, providing opportunities for developing cell encapsulation technologies, biomimetic cellular microenvironments, minimally invasive approaches to surgeries, self-regulated systems, and targeted drug delivery methods. We are engineering biomaterials that are responsive to temperature changes, photo stimuli, and biochemical signals. These materials will be exploited to engineer dynamic bioactive surfaces, build three dimensional cellular microenvironments, and develop targeted drug delivery systems. Molecular mechanisms of cellular responses to environment elasticity Mechanical signals play critical roles in regulating cell behavior and have significant implications for development, disease, and regeneration. These mechanical signals include shear stress, pressure, and elastic properties of the environment. We are particularly interested in cellular responses to environmental elasticity. In the past decade, emerging evidence has suggested that most normal tissue cells probe the elastic properties of their microenvironments, including extracellular matrix, synthetic substrates, and adjacent cells, and respond to the environment stiffness in changing adhesion, proliferation, differentiation, migration, and survival. However, the molecular mechanisms of this mechanical signal transduction remain unknown. We are interested in elucidating the molecular mechanisms of cellular responses to environmental elasticity and the crosstalk between this mechanical signal and biochemical signals. Molecular engineering of subcellularly targeted biosensors and therapeutics The ability of monitoring and manipulating intracellular protein activities in live cells is critical for developing diagnostic and therapeutic technologies for various diseases. It also provides the tools for spatial and temporal analysis of subcellular molecular events in live cells in the context of different cellular microenvironments. Were developing subcellularly targeted biosensors and therapeutics through biomolecular engineering. Both rational design and molecular evolution approaches will be used. Selected Publications 2 “Structure and mechanical properties of genetically engineered protein hydrogels assembled through aggregation of leucine zipper peptide domains” Wei Shen, Julia A. Kornfield, and David A. Tirrell, submitted to Soft Matter . 3 “Tuning the erosion rate of artificial protein hydrogels through control of network topology” Wei Shen, Kechun Zhang , Julia A. Kornfield, and David A. Tirrell, Nature Materials, 5, 153-158, 2006. 4 “ Assembly of an Artificial Protein Hydrogel through Leucine Zipper Aggregation and Disulfide Bond Formation ” Wei Shen, Rob G.H. Lammertink, Jill K. Sakata, Julia A. Kornfield, and David A. Tirrell, Macromolecules, 38 (9), 3909 -3916, 2005. 5 “Kinetics of Hydroxyapatite Precipitation at pH 10 to 11” Chang-Sheng Liu, Yue Huang, Wei Shen, et al. Biomaterials 2001, 22(4): 301-306 6 “Solution Property of Calcium Phosphate Cement Hardening Body” Chang-Sheng Liu, Wei Shen , et al. Materials Chemistry and Physics 1999, 58(1): 78-82 7 “Mechanism of the Hardening Process for a Hydroxyapatite Cement” Chang-Sheng Liu, Wei Shen, Yan-Fang Gu, et al. Journal of Biomedical Materials Research 1997, 35(1):75-80 8 “Effect of Crystal Seeding on the Hydration of Calcium Phosphate Cement” Chang-Sheng Liu and Wei Shen Journal of Materials Science-Materials in Medicin e 1997, 8(12):803-807 9 “Evaluation of the Biocompatibility of a Nonceramic Hydroxyapatite” Chang-Sheng Liu, Weng-Bo Wang, Wei Shen et al. J. Endodontics 1997, 23(8):490-493
the Regents of the University of Minnesota. |
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