Nascent adhesions shorten the period of lamellipodium protrusion through the Brownian ratchet mechanism

Author:

Carney Keith R.12,Khan Akib M.12,Stam Samantha12,Samson Shiela C.12,Mittal Nikhil3,Han Sangyoon J.3,Bidone Tamara C.45ORCID,Mendoza Michelle C.142ORCID

Affiliation:

1. Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112

2. Huntsman Cancer Institute, Salt Lake City, UT 84112

3. Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931

4. Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112

5. Scientific Computing and Imaging Institute, Salt Lake City, UT 84112

Abstract

Directional cell migration is driven by the conversion of oscillating edge motion into lasting periods of leading edge protrusion. Actin polymerization against the membrane and adhesions control edge motion, but the exact mechanisms that determine protrusion period remain elusive. We addressed this by developing a computational model in which polymerization of actin filaments against a deformable membrane and variable adhesion dynamics support edge motion. Consistent with previous reports, our model showed that actin polymerization and adhesion lifetime power protrusion velocity. However, increasing adhesion lifetime decreased the protrusion period. Measurements of adhesion lifetime and edge motion in migrating cells confirmed that adhesion lifetime is associated with and promotes protrusion velocity, but decreased duration. Our model showed that adhesions’ control of protrusion persistence originates from the Brownian ratchet mechanism for actin filament polymerization. With longer adhesion lifetime or increased-adhesion density, the proportion of actin filaments tethered to the substrate increased, maintaining filaments against the cell membrane. The reduced filament-membrane distance generated pushing force for high edge velocity, but limited further polymerization needed for protrusion duration. We propose a mechanism for cell edge protrusion in which adhesion strength regulates actin filament polymerization to control the periods of leading edge protrusion.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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