Elucidating the Impact of Matrix Viscoelasticity on Growth Factor Regulated Cell Fate

Tissue stiffness is known to impact cell growth, death, and function. However, less is known about the effect of the fluid-like properties of tissues on cell fate decisions. This award supports fundamental research to understand how cells sense the fluid-like properties of their environment. The goal is to reveal information about how tissue mechanical properties guide cells to grow, die, or exhibit specialized functions. This information will help to understand how organs and embryos grow, how tissues repair from injury, and how to make artificial organs for replacement therapies. Therefore, the work may provide biomedical and healthcare benefits to society. Research efforts will be integrated with education by hosting undergraduate students in research experiences, developing hands-on activities about tissue mechanics for an undergraduate-level laboratory course, and developing an undergraduate research module for first-year seminar courses. While the effect of tissue elasticity on cell function is well recognized, there is a lack of knowledge regarding the regulation of mechanotransduction pathways by matrix viscoelasticity. To fill this knowledge gap, this project will elucidate how the viscous properties of the extracellular matrix influence cell response to growth factors and will delineate mechanoresponsive pathways regulating how matrix viscoelasticity is sensed by cells to guide cell fate decisions. To achieve this, the research team will develop and characterize viscoelastic materials with tunable elastic and viscous properties. This platform will be used to determine the impact of viscous dissipation on cell proliferation, apoptosis, and differentiation in response to growth factors. Studies will also establish how matrix viscous dissipation regulates cell-matrix adhesion and kinase-mediated signaling pathways. Furthermore, the role of mechanoresponsive signaling molecules in regulation of growth factor receptor signaling and degradation will be examined. By elucidating mechanotransduction mechanisms downstream of matrix viscoelasticity, this work will advance fundamental understanding of how cells respond to the combined effects of growth factors and matrix physical properties. 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.