We propose a new technology for dynamic stem cell culture, using arrays of optically actuated polymer microposts. The polymer structures will be created by replica molding of straight and slanted microposts, made using carbon nanotube (CNT) and silicon master molds. The replica structures will be cast using photoactive liquid crystal elastomers (LCEs). Illumination of the LCE microposts will cause a rapid change in their shape and/or stiffness;and it will be possible to actuate arbitrary areas of posts based on the spot size and intensity of the illumination beam. We will assess cell viability on LCE structures i comparison to conventional poly- dimethylsiloxane (PDMS) structures as a benchmark material, by engineering the geometry and stiffness of the two materials. Using designed arrays of microposts enabling dynamic modulation of rigidity and strain that mimics the amplitude and force of cardiomyocyte beating, we will investigate pathways for mechanically-modulated differentiation of human embryonic stem cells (hESCs) into cardiomyocytes. Thus, we will aim to improve the accuracy and throughput of cardiomyocyte differentiation, and the understanding of how mechanotransduction affects cardiogenic differentiation. Successful development of this novel system would enable further research on mechanotransductive signaling under dynamic control, and possibly the realization of mechanically controlled assays for high-throughput cell culture. 1

Public Health Relevance

Mechanotransduction is innate to the growth and function of cells and tissues, and to the pathology of disease. The novel optically actuated micropost array tool (OAPA) developed in this project will enable improvements in the speed and accuracy of stem cell differentiation, by combining mechanical and chemical factors in a dynamic cell culture environment. Experiments will focus on the targeted differentiation of cardiomyocytes for use in heart regeneration therapy, and the technology could be applied to many other cell types, via fundamental studies of cell behavior, and development of novel instruments for cell analysis and high-throughput differentiation. 1

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL114011-02
Application #
8703172
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Lundberg, Martha
Project Start
2013-08-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$229,077
Indirect Cost
$55,182
Name
Massachusetts Institute of Technology
Department
Type
Schools of Engineering
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Kim, Sanha; Sojoudi, Hossein; Zhao, Hangbo et al. (2016) Ultrathin high-resolution flexographic printing using nanoporous stamps. Sci Adv 2:e1601660
Weng, Shinuo; Shao, Yue; Chen, Weiqiang et al. (2016) Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis. Nat Mater 15:961-967
Zhao, Hangbo; Wie, Jeong Jae; Copic, Davor et al. (2016) High-Fidelity Replica Molding of Glassy Liquid Crystalline Polymer Microstructures. ACS Appl Mater Interfaces 8:8110-7
Taniguchi, Kenichiro; Shao, Yue; Townshend, Ryan F et al. (2015) Lumen Formation Is an Intrinsic Property of Isolated Human Pluripotent Stem Cells. Stem Cell Reports 5:954-962
Chen, Di; Sun, Yubing; Gudur, Madhu S R et al. (2015) Two-bubble acoustic tweezing cytometry for biomechanical probing and stimulation of cells. Biophys J 108:32-42
Chen, Di; Sun, Yubing; Deng, Cheri X et al. (2015) Improving survival of disassociated human embryonic stem cells by mechanical stimulation using acoustic tweezing cytometry. Biophys J 108:1315-7
Shao, Yue; Sang, Jianming; Fu, Jianping (2015) On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology. Biomaterials 52:26-43
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Shao, Yue; Mann, Jennifer M; Chen, Weiqiang et al. (2014) Global architecture of the F-actin cytoskeleton regulates cell shape-dependent endothelial mechanotransduction. Integr Biol (Camb) 6:300-11

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