Cell Matrix Interactions

How do the mechanical properties of the environment influence cell morphology and fate? 

Cell adhesion is a critical stage in the life of adherent cells such as muscle cells, epithelial cells and stem cells. Upon binding to the extra-cellular matrix, elastic stresses are actively generated in the cell by numerous molecular motors (mainly myosin) that locally compress (and globally stretch) the cytoskeleton. By pulling on the environment cells can 'sense' and respond to mechanical properties of their surroundings (for instance the rigidity and topography of the extracellular matrix or the presence of other contractile cells in their vicinity). Indeed, experiments have shown that elastic stresses that develop in the cell cytoskeleton upon cell adhesion feedback on myosin motor activity governing their assembly with actin filaments to form organized muscle-like fibers, called stress-fibers. This creates a mechanical feedback loop between the cell and the environment that affects the morphology, internal structure and eventually the fate of the cell. Using elasticity theory and principles of condensed matter physics we study the dynamics and energetics of cell-matrix interactions, including the reorganization and formation of stress-fibers in the cytoskeleton, anchorage to the extracellular matrix and the accompanying development of the cell shape, both in stationary and migrating cells. To read more about this see the references below. Ref. [1-3] discuss the effects of substrate rigidity and cell shape on the development of acto-myosin stress fibers in cells. Ref [4] analyses the effects of the cell nucleus on the orientation of actomyosin stress fibers around it. Ref. [5-6] present a simple mechanical model of cell spreading dynamics.

Also see news coverage of our work on the mechanics of stem cells here: Hebrew University, Ynet

 

  1. Zemel, A, F Rehfeldt, AEX Brown, DE Discher, and SA SAFRAN. 2010. “Optimal Matrix Rigidity For Stress-Fibre Polarization In Stem Cells.” Nature Physics 6. 468–473. 
  2. Zemel, A, F Rehfeldt, AEX Brown, DE Discher, and SA SAFRAN. 2010. “Cell Shape, Spreading Symmetry, And The Polarization Of Stress-Fibers In Cells.” Journal Of Physics: Condensed Matter 22. IOP Publishing: 194110.
  3. Nisenholz, Noam, Mordechai Botton, and Assaf Zemel. 2014. “Early-Time Dynamics Of Actomyosin Polarization In Cells Of Confined Shape In Elastic Matrices.” Soft Matter 10. Royal Society of Chemistry: 2453–2462.
  4. Zemel, Assaf. 2015. “Active Mechanical Coupling Between The Nucleus, Cytoskeleton And The Extracellular Matrix, And The Implications For Perinuclear Actomyosin Organization.” Soft Matter 11. Royal Society of Chemistry: 2353–2363.
  5. Nisenholz, Noam, Kavitha Rajendran, Quynh Dang, Hao Chen, Ralf Kemkemer, Ramaswamy Krishnan, and Assaf Zemel. 2014. “Active Mechanics And Dynamics Of Cell Spreading On Elastic Substrates.” Soft Matter 10. Royal Society of Chemistry: 7234–7246.
  6. Nisenholz, Noam, Aishwarya Paknikar, Sarah Köster, and Assaf Zemel. 2016. “Contribution Of Myosin Ii Activity To Cell Spreading Dynamics.” Soft Matter 12. Royal Society of Chemistry: 500–507.