A Multiscale Material Approach to Understanding the Effects of Viscoelasticity on Cell Adhesion, Migration, and TGF-beta Activation/Signaling

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Cells are able to sense and react to changes in the mechanical properties of their microenviroment through a process known as mechanotransduction. The effect of the surrounding environment affects cell attachment, migration, proliferation, and differentiation. However, most tissues that include cells do not behave in a simple, elastic fashion. In fact, their properties are generally non-linear and viscoelastic -- meaning that they vary as the tissue is stretched and based on how quickly the force or stretch is applied. Significant research effort is being conducted into the best ways to get cells to develop into healthy tissues for tissue replacement or enhancement. Understanding how cells respond to their surroundings is key to being able to design systems that will optimize these engineered tissues. This project will focus on the effect of the viscoelastic properties of a substrate -- its ability to dissipate energy based on how quickly the force is applied -- on the clustering of a cellular receptor for a common growth factor (TGF-Beta) as well as how cells respond downstream to signals that are generated. In addition to the scientific impact, the project team will focus on training students in a multidisciplinary environment so that they can in the future work effectively on interdisciplinary teams to tackle complex problems at the interface of engineering, materials science, and biomedical science.In order to investigate the nonlinear, viscoelastic substrate variation on fibroblast behavior, three objectives have been established. First, to determine how the viscoelasticity of a developed microgel, colloidal thin film influences fibroblast adhesion, spreading, migration, and myofibroblastic differentiation. Second, to analyze TGF-Beta receptor clustering, activation, and signaling as a function of microgel film viscoelasticity. And, finally, to examine the effect of pre-patterning TGF-Beta receptors on the substrate via DNA origami on cell adhesion, spreading, migration, and myofibroblastic differentiation. The studies will provide new insights into how cells respond to changes in viscoelasticy in their microenvironment.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.