Mechanosensitivity to extracellular mechanical signals is central to many developmental, physiological, and pathological processes, affecting cell functions including growth, migration, differentiation, and apoptosis. Understanding the molecular mechanisms underlying mechanotransduction process rely on tools capable of applying controlled mechanical forces to cells to elicit and assess cellular responses. The goal of this research is to develop a novel ultrasound-based technology, acoustic tweezing cytometry (ATC), as a powerful cell mechanics and mechanobiology tool. We will perform systematic and comprehensive studies to develop innovative ATC platform and characterize subcellular force generation in ATC for mechanical regulation of cells, which will have broad impact on many practical applications as well as scientific investigations. In this research, we will develop and demonstrate the utility of ATC as a novel and practical strategy for stem cell applications, specifically to enable novel advances in human pluripotent stem cell (hPSC) maintenance and understanding of mechanobiology of hPSCs. Capable of replicating themselves while retaining the ability to give rise to any type of specialized cells, hPSCs provide promising sources for disease modeling, drug screenings, and future cell-based therapeutics to treat degenerative diseases such as diabetes mellitus and spinal cord injury. However, controlling hPSC growth remains challenging because present methods to clonally grow hPSCs are inefficient and poorly defined for genetic manipulation and therapeutic purposes. hPSCs are vulnerable to apoptosis upon cellular detachment and dissociation, with a cloning efficiency of dissociated single hPSCs generally < 1%. Therefore, we propose the following specific aims in this research: 1) to develop an innovative ATC technology platform for applying spatiotemporally controlled subcellular mechanical forces; 2) to determine the effects of ATC on the survival and cloning efficiency of hPSCs; and 3) to reveal the mechanisms of ATC stimulation for improving survival and cloning efficiency of hPSCs.

Public Health Relevance

Mechnotransduction is central to many developmental, physiological, and pathological processes and studying mechanotransduction relies on tools for applying mechanical forces to cells to elicit cellular responses. Human pluripotent stem cells (hPSCs) are invaluable tools for studying tissue formation and promising resource for regenerative medicine. This research will develop a novel technology, acoustic tweezing cytometry, as a powerful tool for cell mechanics and mechanobiology studies, and will specifically exploit its application for improving survival threshold and cloning efficiency of (hPSCs), a major challenge limiting their wide applications.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Conroy, Richard
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University of Michigan Ann Arbor
Biomedical Engineering
Schools of Engineering
Ann Arbor
United States
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Topal, Tu?ba; Hong, Xiaowei; Xue, Xufeng et al. (2018) Acoustic Tweezing Cytometry Induces Rapid Initiation of Human Embryonic Stem Cell Differentiation. Sci Rep 8:12977
Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine et al. (2017) Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche. Nat Mater 16:419-425
Xue, Xufeng; Hong, Xiaowei; Li, Zida et al. (2017) Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells through cytoskeletal contractility and YAP activation. Biomaterials 134:22-30
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Shao, Yue; Sang, Jianming; Fu, Jianping (2015) On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology. Biomaterials 52:26-43