Collaborative Research: Microfluidic Investigation on The Effect of Deformation on the Proliferation and Motility of Single Cells

About This Grant

Cells in the human body experience a variety of physical stresses, especially when they move and squeeze through tight spaces. Studies have shown that some cells become stronger after experiencing physical stress. Furthermore, some cells "remember" stressful experiences and change their biological responses as a result. These physical stresses change the physical appearance of the cells, but it is not understood if these physical changes cause biochemical changes inside the cell. The goal of this project is to engineer a specialized set of devices to understand how physical deformation of cells changes their ability to divide and move. These miniaturized devices simulate the tight spaces the cells squeeze through in the human body. These devices have the unique ability to study individual cells and the overall cell population. The cells can be observed over extended periods of time to study the "memory effects" of physical stress, which will improve understanding of how cells adapt and survive in the human body. This research can lead to new insights into how wounds heal, how cancer spreads through the body, and how stem cells move to where they are needed. This project is expected to have a broad impact on inspiring and preparing the next generation of scientists and engineers through research and activities that include middle school outreach, high school research opportunities, and international experiences for undergraduate students. Human cells constantly face various biophysical stresses that lead to increased proliferation and motility. Exposure to biophysical stressors can also result in a memory effect where the enhanced phenotype is retained for several days after the biophysical exposure. However, the relationship between cellular deformation and the resulting biochemical signaling has not been fully elucidated. To address this, a microfluidic deformation platform to mimic physiological cell squeezing will be engineered. This platform will be used to test the hypothesis that biochemical changes drive enhanced proliferation and motility that are governed by growth factor receptor expression and the stemness-dependent PI3K-AKT-mTOR signaling and other proliferation-related pathways. Objective 1 will study how biophysical constriction alters the phenotype of deformed cells that result in enhanced proliferation by pairing a deformation module with a trapping device. This will demonstrate that deformation enhances activation of proliferation-related pathways and that it will exhibit a memory effect in both single cells and the bulk population. Objective 2 will determine how biophysical constriction alters the motility of the cells by pairing the deformation module with a migration device to study one-dimensional single cell migration and the bulk two-dimensional migration. The signaling pathways that govern how deformation enhances cell motility and how that deformation results in a memory effect will be studied. Since cell deformation is vital in processes like wound healing, cancer metastasis, and stem cell homing, gaining a deeper insight into how it primes the cells for increased proliferation and motility is essential for future medical breakthroughs. 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.