Two Distinct Actin Networks Mediate Traction Oscillations to Confer Mechanosensitivity of Focal Adhesions

Event details
Date | 11.07.2017 |
Hour | 11:00 |
Speaker | Prof. Jian Liu, NIH, Bethesda, MD (USA) |
Location | |
Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
Abstract:
Focal adhesions (FAs) are integrin-based transmembrane assemblies that connect the cell with its extracellular matrix (ECM). They are mechanosensors through which cells exert actin cytoskeleton-mediated traction force to sense the ECM stiffness. Interestingly, FA itself is a dynamic structure that adapts its growth in response to mechanical force. It is unclear how the cell manages the plasticity of FA structure and the associated traction force to accurately sense ECM stiffness. Strikingly, FA traction forces oscillate in time and space and govern the cell mechanosensing of ECM stiffness. But precisely how and why the FA traction oscillates is unknown. We develop a model of FA growth that integrates the contributions of branched actin network and stress fibers (SF). Combining with experimental testing, we show that the retrograde flux of branched actin network promotes the proximal growth of the FA, and contributes to a traction peak near the FA distal tip. The resulting traction gradient within the growing FA favors SF formation near the FA proximal end. The SF-mediated actomyosin contractility further stabilizes the FA and generates a second traction peak near the FA center. Formin-mediated SF elongation negatively feeds back with actomyosin contractility, resulting in the central traction peak oscillation. This underpins the observed FA traction oscillation, and importantly, broadens the ECM stiffness range, over which FAs could accurately adapt with traction force generation. Actin cytoskeleton-mediated FA growth and maturation thus culminate with FA traction oscillation to drive efficient FA mechanosensing.
Bio:
Jian Liu graduated from Peking University with a B.S. in chemistry in 2000 and earned his Ph.D. in theoretical chemistry from the University of California, Berkeley in 2005. He completed postdoctoral fellowships at the University of California, San Diego, Center for Theoretical Biological Physics from 2005 to 2007 and at the University of California, Berkeley, Department of Molecular and Cell Biology in the laboratory of George Oster from 2007 to 2009. Dr. Liu joined the NHLBI as a tenure-track Investigator in 2009. Dr. Liu’s laboratory uses the tools of statistical physics to cohere this expanding data set from biological experiments into quantitative models that capture fundamental insights and make concrete predictions about multiple cellular processes, including membrane trafficking, cell motility, and cell division.
Abstract:
Focal adhesions (FAs) are integrin-based transmembrane assemblies that connect the cell with its extracellular matrix (ECM). They are mechanosensors through which cells exert actin cytoskeleton-mediated traction force to sense the ECM stiffness. Interestingly, FA itself is a dynamic structure that adapts its growth in response to mechanical force. It is unclear how the cell manages the plasticity of FA structure and the associated traction force to accurately sense ECM stiffness. Strikingly, FA traction forces oscillate in time and space and govern the cell mechanosensing of ECM stiffness. But precisely how and why the FA traction oscillates is unknown. We develop a model of FA growth that integrates the contributions of branched actin network and stress fibers (SF). Combining with experimental testing, we show that the retrograde flux of branched actin network promotes the proximal growth of the FA, and contributes to a traction peak near the FA distal tip. The resulting traction gradient within the growing FA favors SF formation near the FA proximal end. The SF-mediated actomyosin contractility further stabilizes the FA and generates a second traction peak near the FA center. Formin-mediated SF elongation negatively feeds back with actomyosin contractility, resulting in the central traction peak oscillation. This underpins the observed FA traction oscillation, and importantly, broadens the ECM stiffness range, over which FAs could accurately adapt with traction force generation. Actin cytoskeleton-mediated FA growth and maturation thus culminate with FA traction oscillation to drive efficient FA mechanosensing.
Bio:
Jian Liu graduated from Peking University with a B.S. in chemistry in 2000 and earned his Ph.D. in theoretical chemistry from the University of California, Berkeley in 2005. He completed postdoctoral fellowships at the University of California, San Diego, Center for Theoretical Biological Physics from 2005 to 2007 and at the University of California, Berkeley, Department of Molecular and Cell Biology in the laboratory of George Oster from 2007 to 2009. Dr. Liu joined the NHLBI as a tenure-track Investigator in 2009. Dr. Liu’s laboratory uses the tools of statistical physics to cohere this expanding data set from biological experiments into quantitative models that capture fundamental insights and make concrete predictions about multiple cellular processes, including membrane trafficking, cell motility, and cell division.
Practical information
- Informed public
- Free
Organizer
- Dr. Alexander Verkhovski (Dietler Lab, SB)