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

Abstract

SUMMARY 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.

Frustrated Phagocytic Spreading of J774A-1 Macrophages Ends in Myosin II-Dependent Contraction

“…It has been shown that increasing membrane tension results in numerous intracellular signaling events, including the inhibition of Rac activation and actin assembly (20,39). Our results agree with these findings.…”

“…When we compare the FP spreading dynamics with measurements of cortical tension behavior during traditional phagocytosis reported by Lam et al (17,18) and Herant et al (19), we find that the onset of contraction coincides with points at which tension is likely to increase. This agrees with the finding that frustrated phagocytic spreading by RAW264.7 macrophages slows/halts due to an increase in membrane tension and that tension appears to regulate the actin-machinery-related signal Rac1 (20,21). To further investigate the link between tension and contraction, we subjected the cells to hyperosmotic shock to decrease the membrane cortical tension.…”

“…There is also evidence that increasing membrane tension signals the inhibition of actin assembly (20). Although inhibition of actin assembly may explain why spreading halts leading into late-stage FP, stalled filament growth alone does not explain why actin reorganizes into bundles around the cell perimeter, nor does it explain how the cell is able to exert the contractile stresses we measured using TFM.…”

“…However, there is evidence that membrane tension is also involved in signaling intracellular processes via membrane-associated sensors (39). Moreover, membrane tension has been shown to play a role in phagocytosis-related signaling (20,21). In an extensive effort to mechanically characterize and model phagocytosis, Herant and co-workers (19) argued that membrane cortical tension (which includes both the plasma membrane tension and the tension within the cytoskeletal cortex) can be thought of as being the sum of two components: an elastic component g el , which represents the steady-state elastic buildup of tension within the membrane and cortex, and a viscous component g vis , which accounts for the phagocytes' ability to relieve tension through the unfurling of membrane microfolds and exocytosis.…”

Myosin 1g regulates cytoskeleton plasticity, cell migration, exocytosis, and endocytosis in B lymphocytes

“…Since alterations in adhesion forces, cell spreading and membrane tension have been reported as being responsible for defective cell migration [23][24][25][26], we tested the ability of Myo1g-deficient B cells to migrate toward a chemokine gradient. We used CXCL13 to induce migration of resting B lymphocytes over a fibronectincoated surface in a chemotaxis chamber.…”