Focal adhesion architecture and composition regulate adhesion and traction generation
Abstract/Contents
- Abstract
- Biological systems can sense and respond to a range of mechanical forces that can profoundly affect the forms of developing tissues and the progression of diseases. Even individual cells can recognize mechanical inputs that drive changes in cellular behavior and coordinate cell adhesion and migration. Cells use focal adhesion protein complexes to link the extracellular matrix (ECM) to the actomyosin cytoskeleton, the force bearing and generating network within the cell, allowing for both force sensing and active remodeling of their environment. These complexes include integrins, which are heterodimeric transmembrane proteins that bind to the ECM and recruit focal adhesion proteins that connect to the actin cytoskeleton. However, how force is transmitted through integrins and how cells regulate those forces is not fully understood. We used Förster resonance energy transfer (FRET)-based molecular tension sensors to determine the magnitude and origins of the forces experienced by individual integrins in living cells. These measurements revealed a functional modularity where the number and nature of connections to actin set the force per integrin, while different integrin classes independently controlled adhesion size and ECM ligand specificity. Our single-molecule measurements also revealed the dynamics of force transmission at individual integrins within cellular adhesion complexes. These observations provided a direct test of the predictions of the molecular clutch model, which is commonly used to describe how force is transmitted from the actin cytoskeleton through cellular adhesion complexes. Surprisingly, only a small subset of tension sensors exhibited dynamic loading in contrast to the predications of the clutch model. Instead, we found that the majority of sensors reported constant force magnitudes. We developed a modified model which incorporates the dynamics of the actin cytoskeleton and could reproduce the force plateaus we observe. In total, our observations support a general model for how cells create regulated and dynamic adhesions to the extracellular matrix.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Tan, Steven | |
|---|---|---|
| Degree supervisor | Dunn, Alexander Robert | |
| Thesis advisor | Dunn, Alexander Robert | |
| Thesis advisor | Chaudhuri, Ovijit | |
| Thesis advisor | Sattely, Elizabeth | |
| Degree committee member | Chaudhuri, Ovijit | |
| Degree committee member | Sattely, Elizabeth | |
| Associated with | Stanford University, Department of Chemical Engineering. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Steven John Tan. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Steven Tan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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