Oscillations, waves, and symmetry breaking in cell motility
Abstract/Contents
- Abstract
- Actin-based cell migration depends on the temporal and spatial integration of multiple force-generating systems. Polymerization of the actin network drives protrusion of the cell membrane, and the stretched membrane, in turn, exerts force on the actin network. Myosin contraction of the viscoelastic actin network is balanced by cell-substrate adhesion. The molecular components that contribute to each of these forces - actin-based protrusion, membrane tension, myosin-mediated contraction, and adhesion - have been extensively characterized, but the manner in which they are integrated in vivo to give rise to large-scale emergent properties such as cell shape and movement is not well understood. This thesis describes the role of cell-substrate adhesion in large-scale actin network organization and dynamic cell shape determination. Keratocytes exhibit several non-steady-state behaviors, including oscillatory retraction of the trailing edge, waves of protrusion at the leading edge, and symmetry breaking and motility initiation. I have shown that the mechanical and biochemical properties of adhesions contribute to each of these dynamic behaviors. Oscillatory retraction of the trailing edge emerges in fast-moving, fan-shaped keratocytes and I present evidence consistent with a mechanical model in which elastic coupling between the front of the cell and adhesions in the rear drives oscillations. In contrast, I have found that protrusion waves at the leading edge are likely the result of the biochemical, rather than mechanical, properties of adhesions. Traveling waves emerge at high adhesion strengths and adhesion maturation is required for waving. Mature adhesions have been shown previously to bind several components that contribute to leading edge protrusion, including VASP, a protein that promotes actin polymerization by preventing barbed end capping. Dynamic localization of VASP to the leading edge in waving keratocytes is consistent with a reaction-diffusion model in which global depletion of VASP by mature adhesion, in conjunction with local depletion by the polymerizing actin network, results in lateral propagation of protrusion waves. Finally, I present evidence that suggests that balance between cell-substrate adhesion and myosin contraction sets the mechanical instability threshold above which stationary, radially symmetric keratocytes break symmetry and begin to move. On the whole, the work described here represents significant progress towards elucidating the self-organization principles that underly whole cell migration.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Barnhart, Erin Lynn |
|---|---|
| Associated with | Stanford University, Department of Biochemistry |
| Primary advisor | Theriot, Julie |
| Thesis advisor | Theriot, Julie |
| Thesis advisor | Spudich, James A |
| Thesis advisor | Straight, Aaron, 1966- |
| Advisor | Spudich, James A |
| Advisor | Straight, Aaron, 1966- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Erin Lynn Barnhart. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Ph. D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Erin Lynn Barnhart
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