Model of polarization and bi-stability of cell fragments

¹ Tel Aviv University Sackler Faculty of Medicine
² University of California - Davis

^* To whom correspondence should be addressed. E-mail: michk{at}post.tau.ac.il.

Submitted on April 6, 2007
Revised on May 18, 2007
Accepted on 24 July 2007

	Abstract

Directed cell motility is preceded by cell polarization - development of a front-rear asymmetry of the cytoskeleton and the cell shape. Extensive studies implicated complex spatial-temporal feedbacks between multiple signaling pathways in establishing cell polarity, yet physical mechanisms of this phenomenon remain elusive. Based on observations of lamellipodial fragments of fish keratocyte cells, we suggest a purely thermodynamic (not involving signaling) quantitative model of the cell polarization and bi-stability. The model is based on the interplay between pushing force exerted by F-actin polymerization on the cell edges, contractile force powered by myosin II across the cell, and elastic tension in the cell membrane. We calculate the thermodynamic work produced by these intracellular forces, and show that on the short time scale, the cell mechanics can be characterized by an effective energy profile with two minima that describe two stable states separated by an energy barrier and corresponding to the non-polarized and polarized cells. Cell dynamics implied by this energy profile is bi-stable - the cell is either disc-shaped and stationary, or crescent-shaped and motile - with a possible transition between them upon a finite external stimulus able to drive the system over the macroscopic energy barrier. The model accounts for the observations of the keratocyte fragments' behavior and generates quantitative predictions about relations between the intracellular forces' magnitudes and the cell geometry and motility.

Key Words: actin polymerization, cell motility, cell polarization, cell shape, cytoskeleton, elastic stress