QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 21, Issue 3, 405-417, February 1, 2010

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E09-08-0703v1 21/3/405    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Meili, R. Articles by Lasheras, J. C. PubMed PubMed Citation Articles by Meili, R. Articles by Lasheras, J. C.

Cell Motility

Myosin II Is Essential for the Spatiotemporal Organization of Traction Forces during Cell Motility

Ruedi Meili^*,, Baldomero Alonso-Latorre^,, Juan C. del Álamo, Richard A. Firtel^*,, and Juan C. Lasheras^,,||

*Section of Cell and Developmental Biology, Division of Biological Sciences, Department of Mechanical and Aerospace Engineering, and ^||Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093

Submitted August 17, 2009; Revised November 19, 2009; Accepted November 20, 2009
Monitoring Editor: Carole Parent

Amoeboid motility requires spatiotemporal coordination of biochemical pathways regulating force generation and consists of the quasi-periodic repetition of a motility cycle driven by actin polymerization and actomyosin contraction. Using new analytical tools and statistical methods, we provide, for the first time, a statistically significant quantification of the spatial distribution of the traction forces generated at each phase of the cycle (protrusion, contraction, retraction, and relaxation). We show that cells are constantly under tensional stress and that wild-type cells develop two opposing "pole" forces pulling the front and back toward the center whose strength is modulated up and down periodically in each cycle. We demonstrate that nonmuscular myosin II complex (MyoII) cross-linking and motor functions have different roles in controlling the spatiotemporal distribution of traction forces, the changes in cell shape, and the duration of all the phases. We show that the time required to complete each phase is dramatically increased in cells with altered MyoII motor function, demonstrating that it is required not only for contraction but also for protrusion. Concomitant loss of MyoII actin cross-linking leads to a force redistribution throughout the cell perimeter pulling inward toward the center. However, it does not reduce significantly the magnitude of the traction forces, uncovering a non–MyoII-mediated mechanism for the contractility of the cell.

Co-senior author.

These authors contributed equally to this work.

Address correspondence to: Richard A. Firtel (rafirtel{at}ucsd.edu)

Abbreviations used: F-actin, filamentous actin; MyoII, nonmuscular myosin II complex; MhcA, MyoII heavy chain; MlcE, myoII essential light chain; MlcR, MyoII regulatory light chain; mIcE^–, mlcE null; mhcA^–, mhcA null; wild-type, wild type; V, average velocity of a cell; T, duration of the motility cycle of a cell; T₁, average duration of the protrusion phase; T₂, average duration of the contraction phase; T₃, average duration of the retraction phase; T₄, average duration of the relaxation phase; , average distance traveled by a cell during one motility cycle; L, length of a cell; Us, strain energy deposited by a cell on its substrate; R_UsUs, auto correlation coefficient of the time evolution of Us; R_Lus, cross correlation coefficient of the time evolution of Us; AF, overall positive area flux (rate of area gain) in the front of a cell; AF, overall positive area flux (rate of area gain) in the back of a cell; AF, overall negative area flux (rate of area loss) in the front of a cell; AF, overall negative area flux (rate of area loss) in the back of a cell; AF_def, area flux (rate of area change) of deformation; AF_trans, area flux (rate of area change) of shape-preserving translocation; V_trans, velocity of shape-preserving translocation.