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Joint MNE-EAS Seminar: Dr. Hongyan Yuan, Mechanobiochemical Modeling of Micro-tissue Morphogenesis in Engineered Microenvironments

When: Wednesday, October 7, 2015
11:00 AM - 12:00 PM
Where: Textiles Building 101E
Description: Recent advances in cell biology and three-dimensional (3D) bioprinting technologies have made it possible to create 3D complex functional human tissues/organs. The ability to engineer 3D tissues/organs on demand will have an unprecedented impact in the fields of regenerative medicine and drug discovery. In the United States, about 21 people die each day while waiting for transplants due to the shortage of donated organs. 3D bioprinting of tissues/organs holds great promise for overcoming the present health crisis. In 3D bioprinting, to recapitulate biological functions, the central challenge is to reproduce the complex micro-architecture and micro-morphology of the tissue. Therefore, a thorough understanding of how micro-tissues form in engineered microenvironments is of great importance for the 3D bioprinting approach to succeed.
Tissue/organ morphogenesis is a complex process occurring at multiple scales. Focusing on the whole organ scale, considerable research has been devoted to elucidation of the physical principles underlying the formation of the overall morphologies of organs. In these whole-organ level studies, information at the individual cell level has been homogenized or ignored. At the other extreme of the length scale, the genetic and molecular causes that dictate the tissue/organ formation have been intensively studied. However, at the mesoscopic scale of individual cells, our current understanding of the dynamic processes of micro-tissue morphogenesis is very limited. Mechanobiochemical principles underlying the micro-tissue morphogenesis can help to bridge the gap between the molecular biology and the macroscale tissue/organ formation.
In the present work, a finite element-based computational model to describe and predict the dynamic process of micro-tissue morphogenesis in engineered microenvironments is being developed. We hypothesize that a cell spatially integrates local mechanosensing over the whole-cell scale using continuum mechanics principles. We formulated a mathematical model to describe cell-matrix and cell-cell adhesions, the cell protrusion/retraction, and cytoskeleton contraction in the dynamic process of cell/microtissue morphogenesis. The finite element method was used to numerically solve the evolution equations. Three case studies: single-cell free migration, shape-constrained cell spreading, and cell-pair microtissue formation, were simulated and compared with experimental observations to guide the tuning of the model parameter values. This phenomenological model can help understand how cells, as complex systems, integrate numerous sub-cellular and molecular-scale functions at the whole-cell scale and how distinct cell/microtissue morphologies emerge.
Topical Areas: University Community, Bioengineering, College of Engineering, Mechanical Engineering, Physics