Membrane Tension Maintains Cell Polarity by Confining Signals to the Leading Edge during Neutrophil Migration

Cardiovascular Research Institute and Department of Biochemistry, University of California San Francisco, San Francisco, CA 94143, USA.
Cell (Impact Factor: 32.24). 01/2012; 148(1-2):175-88. DOI: 10.1016/j.cell.2011.10.050
Source: PubMed


Little is known about how neutrophils and other cells establish a single zone of actin assembly during migration. A widespread assumption is that the leading edge prevents formation of additional fronts by generating long-range diffusible inhibitors or by sequestering essential polarity components. We use morphological perturbations, cell-severing experiments, and computational simulations to show that diffusion-based mechanisms are not sufficient for long-range inhibition by the pseudopod. Instead, plasma membrane tension could serve as a long-range inhibitor in neutrophils. We find that membrane tension doubles during leading-edge protrusion, and increasing tension is sufficient for long-range inhibition of actin assembly and Rac activation. Furthermore, reducing membrane tension causes uniform actin assembly. We suggest that tension, rather than diffusible molecules generated or sequestered at the leading edge, is the dominant source of long-range inhibition that constrains the spread of the existing front and prevents the formation of secondary fronts.

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    • "In light of these claims, our results are significant because they illustrate that late-stage contraction occurs even in the absence of any particle cur- vature. There mounting evidence that increased membrane tension may trigger chemical signals within the cell [46] [39] [24] [49]. It is possible that late-stage myosin activity is triggered by a peak in membrane tension occurring as the cell reaches its maximum spreading area. "
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    • "Molecular Biology of the Cell to additional regulation on Cdc42 activity— for example, negative feedback stemming from mechanical tension (Houk et al., 2012). Such regulation is beyond the scope of this work but could be included in an extension of the model that we present here. "
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    • "In recent years it has become clear that not only biochemical signal transmission is the predominant route for cells to communicate but that also changes in membrane's mechanical properties play a pivotal role in information transfer in cells and tissues. In particular, bending of membranes as well as tension in the membrane has been shown to be involved in the cell's behavior such as cell motility or the development and maintenance of its polarity [1]. Vesicle trafficking is also regulated by plasma membrane tension. "
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