Shengyuan Yang, Ph.D. - US grants

CAREER: Micro and Nano Methods to Reveal Cell Sensitivities to Local Stiffness

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."
A class of three-dimensional micro force sensors and a class of substrates with integrated micro force sensors will be developed to measure the cell sensitivities to local stiffness; A class of continuous substrates with stiffness patterns at micro- and nano-meter scales will be developed to study cell sensitivities to local substrate stiffness (SS); A class of substrates with magnetorheological and magnetic fluids will be developed to study cell response to changing SS; Based on the obtained experimental results, a detailed biophysical model will be established at the molecular level to describe the dynamic cell mechanosensitive mechanism and process to SS.

Intellectual Merit: Cell adhesion, spreading, migration, and differentiation have been found to be extremely sensitive to the stiffness of the substrates on which the cells were grown. But the mechanism through which the cells sense the SS locally and how the cells integrate the local SS information and transfer this information into biological behaviors remain largely unclear, which motivated and the issues will be addressed by this proposed research. The successful completion of this project will significantly enhance our understanding of cell mechanosensitivity and mechanotransduction, cell behaviors in tissues, and tissue development. Like the widely used patterning the surface topography and chemistry, the concept of micro- and nano-patterning the stiffness of the substrates, introduced in this project, opens a new paradigm and is transformative for the study of cell and tissue mechanobiology and engineering and its applications.

Broader Impacts: The results to be drawn from the proposed research provide fundamental knowledge for us to realize micromechanical control of cell and tissue development, which has crucial applications in tissue engineering and regenerative medicine. The developed micro and nano methods can be used in or extended to any other studies involving measurements of mechanical properties and interactions, examinations of interfacial phenomena, and fabrications of patterned surfaces. The educational plan will promote the participation of underrepresented groups in science and engineering, quickly disseminate the research advances to broad audiences, result in some of the core curricula and facilities for the new Biomedical Engineering Graduate Program at Florida Tech, and boost cross-disciplinary research and education. Lectures and demonstrations will be given in public venues; Summer camps and short training courses will be organized and a significant number of seats will be reserved for students from underrepresented groups, and three new graduate courses will be offered at Florida Tech; An informal club named ?Closer Interaction? will be established for the students, faculty, and staff from the engineering and biological departments at Florida Tech.

Cell engineering (stem cell technology and cell sorting) has been receiving increased attention due to its wide and promising applications in disease diagnosis and treatment, tissue engineering, and regenerative medicine. The behavioral responses of cells to three-dimensional (3D) micromechanical environments are of special interest in recent years because the environments of cells in vivo are 3D in nature. 3D micromechanical environments are much more challenging to design, fabricate, characterize, and apply for fruitful cell studies and applications compared with the corresponding two-dimensional (2D) ones. The curvature of a 3D substrate on which a cell will be growing is one of the major geometrical parameters of this substrate, and therefore, creating curvature-defined 3D cell culture substrates is crucial for 3D cell mechanobiology and bioengineering. This team has invented a first-ever unique and powerful class of 3D curvature-defined cell culture substrates - micro glass ball embedded gels. This technology opens up countless opportunities for the field of cell and tissue engineering and its biomedical applications. The objective of this NSF I-Corps Teams project is to start the process to promote and commercialize this newly-invented and patented technology.

The class of cell culture substrates, micro glass ball embedded gels, introduced in this NSF I-Corps Teams project provides a unique and useful tool for studying cell and tissue mechanobiological responses to substrate curvatures and local stiffness, and for other related cell and tissue engineering researches and biomedical applications. Specifically, this technology provides the first-ever cell culture substrates with defined curvatures. The effect of substrate curvature is one of the fundamental aspects in the currently cutting-edge and very hot area of research: cell and tissue mechanobiology and bioengineering. This technology also provides the first-ever cell culture substrates with defined nanometer to micrometer scale stiffness patterns. These substrates and the similar ones prepared/fabricated by the same strategy can be used in or extended to any other studies involving micro- and nanocomposites and interfacial phenomena. The method, introduced in this project, to prepare/fabricate micro glass ball embedded gels, opens a new strategy and is transformative for micro- and nanofabrication of even or uneven regular or irregular shaped (substrate) surfaces or arrays or patterns or composites.