$1.35M For New Study of Cell MigrationFischell Department of Bioengineering associate professor Helim Aranda-Espinoza is part of an international team recently awarded a three-year, $1.35 million Human Frontier Science Program (HFSP) research grant for a proposal to study cell migration in complex environments.
HFSP promotes and supports investigators conducting new and fundamental research in biological systems, with particular emphasis on cross-disciplinary and international collaborations. The organization also supports work perceived as cutting-edge or risky due to its novel nature. Aranda-Espinoza and his colleagues received one of 22 Program Grants awarded by the HFSP in 2011. They were selected from a field of 650 applicants worldwide.
Cells use different techniques to move through their environments. Aranda-Espinoza's team is focusing on "blebbing," in which pressure causes part of a cell's outer plasma membrane to push forward, creating a protrusion (the "bleb") and detaching itself from its cytoskeleton in the process.
Traditionally, this behavior has been associated with impending cell death, but more recent studies have discovered that some cells—including certain cancer cells—use it as a means of getting around. In the case of blebbing, the detachment of the plasma membrane is reversible. It is believed that as the bleb and cytoskeleton expand and contract, detaching and reattaching, the cell moves forward.
The team will work to define the differences in the cellular reactions that drive blebbing versus other types of cell motility. Investigators will also determine how multiple factors, such as the geometry, adhesiveness and stiffness of the cells' environments and the presence of external loads, affect their mechanical behavior.
"We'll be using zebrafish germ cells and mouse leukoytes [white blood cells] as in vivo model systems that represent the blebbing cells," Aranda-Ezspinoza explains. "These and other model cell types will be subjected to genetic, pharmacological and environmental manipulations that will uncover their range of plasticity in force generation."
The team will use newly-developed techniques to quantitatively measure forces and dynamically visualize the blebbing cells' cytoskeletal components, their behavior under a wide range of conditions, and their movement. Forces exerted by the cell will be recorded quantitatively. The data collected will be analyzed in light of physical models.
"The integration of experimental data and theoretical modeling should ultimately lead to the development of a universal model that allows researchers to predict the migratory strategy of a cell as a function of its internal and environmental conditions," says Aranda-Espinoza.
Aranda-Espinoza's collaborators on the project, titled "Cell Migration in Complex Environments: From In Vivo Experiments to Theoretical Models," include Eres Raz (Institute of Cell Biology, Germany), Pierre Sens (Laboratoire de Physico-Chemie Theorique, France), and Michael Sixt (Institute of Science and Technology, Austria).
Published August 25, 2011