Bipedal Locomotion in Crawling Cells

Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
Biophysical Journal (Impact Factor: 3.97). 03/2010; 98(6):933-42. DOI: 10.1016/j.bpj.2009.10.058
Source: PubMed


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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    • "We further assume that some internal mechanism (stiffness of the cell cortex [45] [46] [47] [48] [49] [50], osmotic pressure actively controlled by the channels and pumps on the cell membrane [51] [52], etc.) maintains a given size L 0 = l + − l − of the cell. Therefore the stress at the edges must be the same σ(l − (t), t) = σ(l + (t), t) = σ 0 , where σ 0 (t) is then an unknown function. "
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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.
    Mathematics and Mechanics of Solids 01/2015; DOI:10.1177/1081286515588675 · 1.30 Impact Factor
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    • "For wildtype and scrA − cells, we found that the cell length and strain energy oscillations are highly correlated, suggesting that the regulation of the cycle depends on the ability of the cell to modulate its length and to generate traction stresses. We confirmed that the average period of the oscillations in the cell length (and strain energy) for wild-type and scrA − cells is inversely proportional to the cell's average migration speed, in agreement with our previous findings for cell movement on gelatin substrates (del Álamo et al., 2007; Meili et al., 2010) and with experimental measurements and theoretical models obtained for crawling keratocytes (Barnhart et al., 2010). This correlation is also consistent with the view that the average speed of migration of the cell is determined by the frequency at which it can perform its motility cycle. "
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    ABSTRACT: Cell migration requires a tightly regulated, spatiotemporal coordination of underlying biochemical pathways. Crucial to cell migration is SCAR/WAVE-mediated dendritic F-actin polymerization at the cell's leading edge. Our goal is to understand the role the SCAR/WAVE complex plays in the mechanics of amoeboid migration. To this aim, we measured and compared the traction stresses exerted by Dictyostelium cells lacking the SCAR/WAVE complex proteins PIR121 (pirA(-)) and SCAR (scrA(-)) with those of wild-type cells while they were migrating on flat, elastic substrates. We found that, compared to wild type, both mutant strains exert traction stresses of different strengths that correlate with their F-actin levels. In agreement with previous studies, we found that wild-type cells migrate by repeating a motility cycle in which the cell length and strain energy exerted by the cells on their substrate vary periodically. Our analysis also revealed that scrA(-) cells display an altered motility cycle with a longer period and a lower migration velocity, whereas pirA(-) cells migrate in a random manner without implementing a periodic cycle. We present detailed characterization of the traction-stress phenotypes of the various cell lines, providing new insights into the role of F-actin polymerization in regulating cell-substratum interactions and stresses required for motility.
    Molecular biology of the cell 09/2011; 22(21):3995-4003. DOI:10.1091/mbc.E11-03-0278 · 4.47 Impact Factor
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