The Fraley Lab is advancing understanding of how cells migrate in physiologically relevant 3D environments thoughthe development of novel microscopy techniques, 3D matrix engineering, and molecular engineering.
Understanding how living cells migrate in reliable and orchestrated ways is essential to understanding the most fundamental functions of life. Cell migration is a complex behavior that emerges from the interactions of tens of thousands of molecular parts. Many of these molecular parts and the processes they carry out have been identified, thanks to advances in microscopy. In fact, progress in migration research has always been tied to progress in microscopic imaging techniques, and open questions in the field have driven the development of novel quantitative imaging methods. Still much of what we know is limited to the context of cell migration on artificial 2D environments, for example glass, precisely because of its compatibility with imaging. We are working to move migration research into the third dimension.
Understanding how living cells migrate in reliable and orchestrated ways is essential to understanding the most fundamental functions of life. Cell migration is a complex behavior that emerges from the interactions of tens of thousands of molecular parts. Many of these molecular parts and the processes they carry out have been identified, thanks to advances in microscopy. In fact, progress in migration research has always been tied to progress in microscopic imaging techniques, and open questions in the field have driven the development of novel quantitative imaging methods. Still much of what we know is limited to the context of cell migration on artificial 2D environments, for example glass, precisely because of its compatibility with imaging. We are working to move migration research into the third dimension.
Cancer cell Vasculogenic mimicry
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By developing a novel 3D collagen matrix engineering technique, we have discovered that specific matrix architectures force cancer cells to alter their gene expression and migration behavior. The result is a switch from single to collective migration and the development of vascular-like structures. This cancer cell phenotype, known as vasculogenic mimicry, has been observed in clinical biopsies in over 16 tumor types and is associated with metastatic progression. The novel gene signature we discovered predicts metastasis in clinical data across six different tumor types. Research positions are available on this project.
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Mechanics of Migration
Since all eukaryotic cells share the same fundamental motility machinery, how do different cell types tune their machinery to achieve different migration behaviors? How does a 3D environment direct cell migration behavior differently than a 2D environment? We are developing a new microscopy platform that will enable us to answer these questions. Research positions are available on this project.
A fibrosarcoma cell pulling itself through a 3D collagen matrix. Beads attached to the collagen are tracked to measure cell traction and matrix remodeling.
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Our custom high-throughput Nikon microscope collects migration data on 300 individual cells every 2 minutes.
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A fibrosarcoma cell lacking the mechanosensory protein Zyxin migrates in a persistent random-walk fashion on a two-dimensional collagen coated petri dish, in the same way as the wild type cell shown in this video.
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A fibrosarcoma cell lacking the mechanosensory protein Zyxin migrates very differently in a 3D collagen matrix. Migration has become highly oscillatory, periodic, and one-dimensional in response to a change in the physical context of the extracellular matrix.
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SI Fraley, et.al., Nature Cell Biology, 2010
SI Fraley, et.al., Nature Cell Biology, 2011
SI Fraley, et.al., Nature Communications, 2012
SI Fraley, et.al., Nature Cell Biology, 2011
SI Fraley, et.al., Nature Communications, 2012