ERI: Investigating the Continuum of Cell Spheroid Biomechanical Behavior with Spheroid Size

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This Engineering Research Initiation (ERI) grant supports research to increase our knowledge of how human bodies work and to increase the power of tissue engineering. Tissue engineering includes growing skin, muscle, and other tissues in a laboratory to use in repairing the body. Other industries such as automobile manufacturing use computer simulations to design safe and effective products. Unfortunately, tissue engineering cannot do this yet due to the complexity of growing human tissues. This project supports fundamental research into designing and predicting the mechanical stiffness of engineered tissues. This will make it easier to build tissues which are mechanically strong enough to use in the body. The work has the potential to benefit society by improving human health and broadens participation in scientific research by involving diverse undergraduate students from in research experiments and sharing their experience with peers.Better predictive modeling and rational design of engineered biomaterials would help advance the field of tissue engineering. However, natural and engineered tissues are incredibly complex, and a unified biomechanical theory that captures observed tissue mechanics across length scales has not yet been developed. An important step is understanding the mechanical behavior of simpler multicellular systems that partially recreate biological complexity. This project will fill in a gap in knowledge around the critical biomechanical transition zone between single cells and multicellular aggregates that approach the tissue level and provide insights for theoretical modeling of multicellular biomechanical systems. The research team will use microfluidics to systematically measure the viscoelastic mechanical properties of cell spheroids ranging in size from single cells (10 micrometers in diameter) up to mesoscale multicellular spheroids (1 mm) and create a finite element model that captures the observed spheroid biomechanics in flow conditions. These experimental and modeling tools will be used to investigate the contributions of individual cells and cell-cell adhesions to the biomechanics of spheroids of different sizes, cell stiffnesses, and adhesion strengths.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.