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Research Papers

Cell Crawling Assisted by Contractile Stress Induced Retraction

[+] Author and Article Information
Sitikantha Roy, Feng Miao

Department of Mechanical Engineering, University of Colorado, Boulder, CO 80309

H. Jerry Qi1

Department of Mechanical Engineering, University of Colorado, Boulder, CO 80309qih@colorado.edu

1

Corresponding author.

J Biomech Eng 132(6), 061005 (Apr 21, 2010) (8 pages) doi:10.1115/1.4001074 History: Received November 03, 2009; Revised January 18, 2010; Posted January 21, 2010; Published April 21, 2010; Online April 21, 2010

Cell locomotion is a result of a series of synchronized chemo-mechanical processes. Crawling-type cell locomotion consists of three steps: protrusion, translocation, and retraction. Previous works have shown that both protrusion and retraction can produce cell movement. For the latter, a cell derives its propulsive force from retraction induced protrusion mechanism, which was experimentally verified by Chen (1979, “Induction of Spreading During Fibroblast Movement,” J. Cell Biol., 81, pp. 684–691). In this paper, using finite element method, we take a computational biomimetic approach to study cell crawling assisted by contractile stress induced de-adhesion at the rear of the focal adhesion zone (FAZ). We assume the formation of the FAZ is driven by receptor-ligand bonds and nonspecific interactions. The contractile stress is generated due to the molecular activation of the intracellular actin-myosin machinery. The exerted contractile stress and its time dependency are modeled in a phenomenological manner as a two-spring mechanosensor proposed by Schwarz (2006, “Focal Adhesions as Mechanosensors: The Two-Spring Model,” BioSystems, 83(2–3), pp. 225–232). Through coupling the kinetics of receptor-ligand bonds with contractile stress, de-adhesion can be achieved when the stall value of the contractile stress is larger than a critical one. De-adhesion at the rear end of the FAZ causes a redistribution of elastic energy and induces cell locomotion. Parametric studies were conducted to investigate the connection between the cell locomotion speed and stall stress, and receptor-ligand kinetics. Finally, we provide a scaling relationship that can be used to estimate the cell locomotion speed.

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Copyright © 2010 by American Society of Mechanical Engineers
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Figures

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Figure 1

A schematic of the cell-substrate attachment through the receptor-ligand bond (18). The right most (front) and left most (rear) nodes in the FAZ are indicated. An actin-myosin machinery that generates contractile stress is also shown schematically (1).

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Figure 2

The schematics of the two-spring model proposed by Schwarz (15)

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Figure 3

The snapshots of the cell crawling. t1=7500 s is the total step time for step I. Contractile stress starts to act at the beginning of step II (t−t1=0). Points 1, 2, and 3 are fixed points on the cell membrane, indicating a significant movement of the cell.

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Figure 4

(a) The contact length evolution with time for the typical case. Time is measured from the beginning of the simulation. Three zones are indicated in the figure, corresponding to A: spreading, B: transition, and C: constant motion; (b) the instantaneous speed versus time. Time (t−t1) measured in step II is used for clarity. t1=7500 s is the total time of step I.

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Figure 5

The contractile fiber stress (σsc), vertical distance (h), and bond density (Nb) evolution with time (for point 1)

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Figure 6

The evolutions of (a) Nb and specific stress (Nbfspc), and (b) the total vertical contact stress as functions of the vertical distance

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Figure 7

The dependence of cell locomotion speed on (a) tk, (b) σ0, and (c) x2

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Figure 8

Scaling relationship between V and tk, σ0, and x2: (a) V versus (tk+a1)−1, where a1=4.0 is a fitting parameter; (b) ln (V) versus (σ0+B); and (c) ln (V) versus x2

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