Membrane Tension in Rapidly Moving Cells Is Determined by Cytoskeletal Forces

Lieber, Arnon D.; Yehudai‐Resheff, Shlomit; Barnhart, Erin L.; Theriot, Julie A.; Keren, Kinneret

doi:10.1016/j.cub.2013.05.063

Cited by 240 publications

(295 citation statements)

References 44 publications

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“…How the distribution of traction forces regulates the shape of the leading edge is another interesting question. The plasma membrane tension of keratocytes is not uniform throughout the cell (Lieber et al, 2013(Lieber et al, , 2015. It is thus possible that the membrane tension around the rear left and right ends, where high traction forces are exerted, is A.…”

Section: Discussionmentioning

confidence: 99%

Shape and Area of Keratocytes Are Related to the Distribution and Magnitude of Their Traction Forces

Sonoda

Okimura

Iwadate

2016

Cell Struct. Funct.

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ABSTRACT. Fish epidermal keratocytes maintain an overall fan shape during their crawling migration. The shape-determination mechanism has been described theoretically and experimentally on the basis of graded radial extension of the leading edge, but the relationship between shape and traction forces has not been clarified. Migrating keratocytes can be divided into fragments by treatment with the protein kinase inhibitor staurosporine. Fragments containing a nucleus and cytoplasm behave as mini-keratocytes and maintain the same fan shape as the original cells. We measured the shape of the leading edge, together with the areas of the ventral region and traction forces, of keratocytes and mini-keratocytes. The shapes of keratocytes and mini-keratocytes were similar. Mini-keratocytes exerted traction forces at the rear left and right ends, just like keratocytes. The magnitude of the traction forces was proportional to the area of the keratocytes and mini-keratocytes. The myosin II ATPase inhibitor blebbistatin decreased the forces at the rear left and right ends of the keratocytes and expanded their shape laterally. These results suggest that keratocyte shape depends on the distribution of the traction forces, and that the magnitude of the traction forces depends on the area of the cells.

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Section: Discussionmentioning

confidence: 99%

Shape and Area of Keratocytes Are Related to the Distribution and Magnitude of Their Traction Forces

Sonoda

Okimura

Iwadate

2016

Cell Struct. Funct.

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“…There is evidence that this membrane tension is important for driving cell migration both in vitro and in vivo (46,47,65). Chemically reducing membrane tension may accelerate cell spreading and lamellipodial extension (19), whereas increasing membrane tension by hypotonic treatment may cause lamellipodial and filopodial retraction (66).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, we concluded that MLCK deletion led to decreased membrane tension. (18,45,47), we speculated that the membrane skeleton was impaired after MLCK deletion. The bleb formation in suspended MLCK-deficient cells also supports this speculation because the incomplete formation of the cytoskeleton underneath the membrane causes membranous blebs (48).…”

Section: Characterization Of Mlck-deficientmentioning

confidence: 99%

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Myosin Light Chain Kinase (MLCK) Regulates Cell Migration in a Myosin Regulatory Light Chain Phosphorylation-independent Mechanism

Chen

Tao

Wen

et al. 2014

Journal of Biological Chemistry

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Background: MLCK in cell migration remains controversial. Results: MLCK deletion causes enhanced cell protrusion along with a reduction of membrane tension and is rescued by kinase-dead MLCK or five-DFRXXL motif. Conclusion: MLCK regulates cell migration not by myosin regulatory light chain phosphorylation but possibly through a membrane tension-based mechanism. Significance: Our results shed light on a novel regulatory mechanism of protrusion during cell migration.

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“…It is known that ENTH of epsin-1 binds specifically to the receptor lipid PtdIns(4,5)P 2 (20 -22), resulting in tubulation or even vesiculation (23,24) as a result of membrane bending. Upon binding to PtdIns(4,5)P 2 an additional ␣-helix, referred to as helix-0 (amino acids [3][4][5][6][7][8][9][10][11][12][13][14][15] at the N terminus of ENTH, is formed. This newly formed helix-0 inserts into the inner monolayer of the plasma membrane resulting in an asymmetry that produces membrane curvature (25,26).…”

mentioning

confidence: 99%

Epsin N-terminal Homology Domain (ENTH) Activity as a Function of Membrane Tension

Gleisner

Kroppen

Fricke

et al. 2016

Journal of Biological Chemistry

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The epsin N-terminal homology domain (ENTH) is a major player in clathrin-mediated endocytosis. To investigate the influence of initial membrane tension on ENTH binding and activity, we established a bilayer system based on adhered giant unilamellar vesicles (GUVs) to be able to control and adjust the membrane tension covering a broad regime. The shape of each individual adhered GUV as well as its adhesion area was monitored by spinning disc confocal laser microscopy. Control of in a range of 0.08-1.02 mN/m was achieved by altering the Mg 2؉ concentration in solution, which changes the surface adhesion energy per unit area of the GUVs. Specific binding of ENTH to phosphatidylinositol 4,5-bisphosphate leads to a substantial increase in adhesion area of the sessile GUV. At low tension (<0.1 mN/m) binding of ENTH can induce tubular structures, whereas at higher membrane tension the ENTH interaction deflates the sessile GUV and thereby increases the adhesion area. The increase in adhesion area is mainly attributed to a decrease in the area compressibility modulus K A . We propose that the insertion of the ENTH helix-0 into the membrane is largely responsible for the observed decrease in K A , which is supported by the observation that the mutant ENTH L6E shows a reduced increase in adhesion area. These results demonstrate that even in the absence of tubule formation, the area compressibility modulus and, as such, the bending rigidity of the membrane is considerably reduced upon ENTH binding. This renders membrane bending and tubule formation energetically less costly.Clathrin-mediated endocytosis is one of the key metabolic pathways for the uptake of macromolecules into eukaryotic cells (1-4). Driven by a chain of remodeling events and an elaborate set of proteins acting in an orchestrated manner, an almost flat patch of plasma membrane is transformed into a closed, cargo-containing vesicle. As plasma membrane shape transformation is associated with significant local bending of the membrane, the process is highly sensitive to lateral membrane tension. Plasma membrane tension originates from two primary sources; that is, hydrostatic pressure across the lipid bilayer and cytoskeleton-membrane adhesion (5). Depending on the cell type, plasma membrane tensions span a range of roughly 0.003-0.45 mN/m (5-8). Even though it had become clear already in the late 1990s that tension plays a role in exoand endocytosis (9, 10), only in recent years has significant evidence been accumulated that membrane tension is of utmost importance for processes that rely on membrane remodeling (11-14). Cells actively maintain and regulate their membrane tension and use it to control exo-and endocytosis (15). In K562 cells it has been reported that endocytosis is completely suppressed under hypoosmotic conditions (16). Generally, high lateral membrane tension suppresses membrane deformation as both stretching the lipid bilayer and opening bonds between the cytoskeleton and the plasma membrane requires a large amount of energy (17).One protein...

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Membrane Tension in Rapidly Moving Cells Is Determined by Cytoskeletal Forces

Abstract: We find that the membrane tension in rapidly moving keratocytes is primarily determined by a mechanical force balance between the cell membrane and cytoskeletal forces. Our results highlight the role of membrane tension as a global mechanical regulator of cell behavior.

Cited by 240 publications

References 44 publications

Shape and Area of Keratocytes Are Related to the Distribution and Magnitude of Their Traction Forces

Shape and Area of Keratocytes Are Related to the Distribution and Magnitude of Their Traction Forces

Myosin Light Chain Kinase (MLCK) Regulates Cell Migration in a Myosin Regulatory Light Chain Phosphorylation-independent Mechanism

Epsin N-terminal Homology Domain (ENTH) Activity as a Function of Membrane Tension

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