Bipedal locomotion in crawling cells.

Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
Biophysical Journal (Impact Factor: 3.83). 03/2010; 98(6):933-42. DOI: 10.1016/j.bpj.2009.10.058
Source: PubMed

ABSTRACT Many complex cellular processes from mitosis to cell motility depend on the ability of the cytoskeleton to generate force. Force-generating systems that act on elastic cytoskeletal elements are prone to oscillating instabilities. In this work, we have measured spontaneous shape and movement oscillations in motile fish epithelial keratocytes. In persistently polarized, fan-shaped cells, retraction of the trailing edge on one side of the cell body is out of phase with retraction on the other side, resulting in periodic lateral oscillation of the cell body. We present a physical description of keratocyte oscillation in which periodic retraction of the trailing edge is the result of elastic coupling with the leading edge. Consistent with the predictions of this model, the observed frequency of oscillation correlates with cell speed. In addition, decreasing the strength of adhesion to the substrate reduces the elastic force required for retraction, causing cells to oscillate with higher frequency at relatively lower speeds. These results demonstrate that simple elastic coupling between movement at the front of the cell and movement at the rear can generate large-scale mechanical integration of cell behavior.

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    ABSTRACT: Modeling cell movement is a challenging task since the motility machinery is highly complex. Moreover, there is a rather broad diversity of different cell types. In order to obtain insights into generic features of the motility mechanisms of several distinct cell types, we propose a modular approach that starts with a minimal model, consisting of a phase field description of the moving cell boundary and a simplified internal dynamics. We discuss how this starting point can be extended to increase the level of detail, and how the internal dynamics “module” can be changed/adjusted to properly model various cell types. The former route allows studying specific processes involved in cell motility in the framework of a self-organized moving domain, and the latter might permit to put different cellular motility mechanisms into a unified framework.
    The European Physical Journal Special Topics 06/2014; 223(7):1265-1277. DOI:10.1140/epjst/e2014-02190-2 · 1.76 Impact Factor
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    ABSTRACT: The motor part of a crawling eukaryotic cell can be represented schematically as an active continuum layer. The main active processes in this layer are protrusion, originating from non-equilibrium polymerization of actin fibers, contraction, induced by myosin molecular motors and attachment due to active bonding of trans-membrane proteins to a substrate. All three active mechanisms are regulated by complex signaling pathways involving chemical and mechanical feedback loops whose microscopic functioning is still poorly understood. In this situation, it is instructive to take a reverse engineering approach and study a problem of finding the spatial organization of standard active elements inside a crawling layer ensuring an optimal cost-performance trade-off. In this paper we assume that (in the range of interest) the energetic cost of self-propulsion is velocity independent and adopt, as an optimality criterion, the maximization of the overall velocity. We then choose a prototypical setting, formulate the corresponding variational problem and obtain a set of bounds suggesting that radically different spatial distributions of adhesive complexes would be optimal depending on the domineering active mechanism of self-propulsion. Thus, for contraction-dominated motility, adhesion has to cooperate with 'pullers' which localize at the trailing edge of the cell, while for protrusion-dominated motility it must conspire with 'pushers' concentrating at the leading edge of the cell. Both types of crawling mechanisms were observed experimentally.


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