Cell Mechanosensation

 

 

Cells interact with and adapt to their environment.  For example, stem cells adhering to surfaces of different stiffness differentiate into distinct lineages. Similarly, clusters of cells implanted in 3D gels are more likely to disorganize and break apart, a process related to cancer metastasis, if the gel is stiff.

 

Traditionally, biological systems have been considered from a chemical or biochemical perspective.  Research has focused on identifying the chemical reactions that occur, and the enzyme catalysts that control them.  The importance of mechanical influences thus represents a shift in how we think about biological systems.  This new field of mechanobiology has attracted attention from experimentalists and theorists alike. 

 

My work on this subject has focused on understanding how cells sense and react to their mechanical environment, particularly how mechanosensation at the molecular scale can lead to emergent properties at larger scales.

 

Example

 

 

 

Movie 1. (Click on image, or here to play)  A crawling cell slides across a surface, forming localized adhesions while its length oscillates.  This simulation was made by Dr. Calina Copos, and reproduces experimental observations made in the del Alamo lab.  Read the whole story in publication 1, below.

Current Publications Relating to Cell Mechanosensation

 

 

1. Copos, C. A., S. Walcott, J. C. del Alamo, E. Bastounis, A. Mogilner and R. D. Guy, Mechanosensitive adhesion explains stepping motility in amoeboid cells.  Biophysical Journal, Volume 112, pages 2672-2682, 2017.  PDF

 

2. Kim, D-H., Katau, S. B., Feng. Y., Walcott, S., Sun, S. X., Longmore, G. D., Wirtz, D., Actin cap associated focal adhesions and their distinct role in cellular mechanosensing. Scientific Reports, Volume 2, Article number 555, 2012.  PDF

 

3. Walcott, S., Kim, D-H., Wirtz, D., Sun, S. X. Nucleation and decay initiation are the stiffness sensitive phases of focal adhesion maturation. Biophysical Journal, Volume 101, pages 2919-2928, 2011.  PDF

4. Harland, B, Walcott, S., Sun, S. X., Adhesion dynamics and durotaxis in migrating cells. Physical Biology, Volume 8, Article number 015011, 2011.  PDF

5. Walcott, S, Sun, S. X., Active force generation in cross-linked filament bundles without motor proteins. Physical Review E, Volume 82, Article number 050901, 2010.  PDF

6. (Invited Commentary) Sun, S. X., Walcott, S., Repairing the sense of touch. Current Biology, Volume 20, pages R895-896, 2010.  PDF

7. (Review Article) Sun, S. X., Walcott, S., Wolgemuth, C. W., Cytoskeletal cross-linking and bundling in motor-independent contraction. Current Biology, Volume 20, pages R649-54, 2010. PDF

 

8. Walcott, S, Sun, S. X., A mechanical model of actin stress fiber formation and substrate elasticity sensing in adherent cells.
Proceedings of the National Academy of Sciences, Volume 107, pages 7757-62, 2010.  PDF

 

9. Srinivasan, M., Walcott, S., Binding site models of friction due to the formation and rupture of bonds: state-function formalism, force velocity relations, response to slip velocity transients, and slip stability.
Physical Review E, Volume 80, pages 046124, 2009. PDF

 

10. Walcott, S., The load dependence of rate constants. Journal of Chemical Physics. Volume 128, pages 215101, 2008.  PDF

 

Collaborators

 

Ben Harland

Dong-Hwee Kim

Sean Sun

Manoj Srinivasan

Charles Wolgemuth

Denis Wirtz

Juan Carlos del Alamo

Bob Guy

Alex Mogilner

Calina Copos