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• W3013611737 abstract "•Traction forces correlate with the distance from the center to the edge of the cell•Analysis of edge and stress dynamics suggests that stress triggers edge retraction•Unlike traction stress, actin flow correlates with distance only during retraction•Simple model reproduces force-distance relationship Traction forces are generated by cellular actin-myosin system and transmitted to the environment through adhesions. They are believed to drive cell motion, shape changes, and extracellular matrix remodeling [1Schwarz U.S. Gardel M.L. United we stand: integrating the actin cytoskeleton and cell-matrix adhesions in cellular mechanotransduction.J. Cell Sci. 2012; 125: 3051-3060Crossref PubMed Scopus (256) Google Scholar, 2Polacheck W.J. Chen C.S. Measuring cell-generated forces: a guide to the available tools.Nat. Methods. 2016; 13: 415-423Crossref PubMed Scopus (291) Google Scholar, 3Nerger B.A. Siedlik M.J. Nelson C.M. Microfabricated tissues for investigating traction forces involved in cell migration and tissue morphogenesis.Cell. Mol. Life Sci. 2017; 74: 1819-1834Crossref PubMed Scopus (14) Google Scholar]. However, most of the traction force analysis has been performed on stationary cells, investigating forces at the level of individual focal adhesions or linking them to static cell parameters, such as area and edge curvature [4Aratyn-Schaus Y. Gardel M.L. Transient frictional slip between integrin and the ECM in focal adhesions under myosin II tension.Curr. Biol. 2010; 20: 1145-1153Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 5Rape A.D. Guo W.H. Wang Y.L. The regulation of traction force in relation to cell shape and focal adhesions.Biomaterials. 2011; 32: 2043-2051Crossref PubMed Scopus (222) Google Scholar, 6Oakes P.W. Banerjee S. Marchetti M.C. Gardel M.L. Geometry regulates traction stresses in adherent cells.Biophys. J. 2014; 107: 825-833Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar, 7Murrell M. Oakes P.W. Lenz M. Gardel M.L. Forcing cells into shape: the mechanics of actomyosin contractility.Nat. Rev. Mol. Cell Biol. 2015; 16: 486-498Crossref PubMed Scopus (331) Google Scholar, 8Kassianidou E. Brand C.A. Schwarz U.S. Kumar S. Geometry and network connectivity govern the mechanics of stress fibers.Proc. Natl. Acad. Sci. USA. 2017; 114: 2622-2627Crossref PubMed Scopus (34) Google Scholar, 9Wu Z. Plotnikov S.V. Moalim A.Y. Waterman C.M. Liu J. Two distinct actin networks mediate traction oscillations to confer focal adhesion mechanosensing.Biophys. J. 2017; 112: 780-794Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 10Vianay B. Senger F. Alamos S. Anjur-Dietrich M. Bearce E. Cheeseman B. Lee L. Théry M. Variation in traction forces during cell cycle progression.Biol. Cell. 2018; 110: 91-96Crossref PubMed Scopus (33) Google Scholar]. It is not well understood how traction forces are related to shape changes and motion, e.g., forces were reported to either increase or drop prior to cell retraction [11Doyle A. Marganski W. Lee J. Calcium transients induce spatially coordinated increases in traction force during the movement of fish keratocytes.J. Cell Sci. 2004; 117: 2203-2214Crossref PubMed Scopus (62) Google Scholar, 12Lombardi M.L. Knecht D.A. Dembo M. Lee J. Traction force microscopy in Dictyostelium reveals distinct roles for myosin II motor and actin-crosslinking activity in polarized cell movement.J. Cell Sci. 2007; 120: 1624-1634Crossref PubMed Scopus (82) Google Scholar, 13Ji L. Lim J. Danuser G. Fluctuations of intracellular forces during cell protrusion.Nat. Cell Biol. 2008; 10: 1393-1400Crossref PubMed Scopus (142) Google Scholar, 14Tanimoto H. Sano M. A simple force-motion relation for migrating cells revealed by multipole analysis of traction stress.Biophys. J. 2014; 106: 16-25Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 15Barnhart E. Lee K.C. Allen G.M. Theriot J.A. Mogilner A. Balance between cell-substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes.Proc. Natl. Acad. Sci. USA. 2015; 112: 5045-5050Crossref PubMed Scopus (71) Google Scholar]. Here, we analyze the dynamics of traction forces during the protrusion-retraction cycle of polarizing fish epidermal keratocytes and find that forces fluctuate together with the cycle, increasing during protrusion and reaching maximum at the beginning of retraction. We relate force dynamics to the recently discovered phenomenological rule [16Raynaud F. Ambühl M.E. Gabella C. Bornert A. Sbalzarini I.F. Meister J.-J. Verkhovsky A.B. Minimal model for spontaneous cell polarization and edge activity in oscillating, rotating and migrating cells.Nat. Phys. 2016; 12: 367-373Crossref Scopus (23) Google Scholar] that governs cell-edge behavior during keratocyte polarization: both traction forces and probability of switch from protrusion to retraction increase with the distance from the cell center. Diminishing forces with cell contractility inhibitor leads to decreased edge fluctuations and abnormal polarization, although externally applied force can induce protrusion-retraction switch. These results suggest that forces mediate distance sensitivity of the edge dynamics and organize cell-edge behavior, leading to spontaneous polarization. Actin flow rate did not exhibit the same distance dependence as traction stress, arguing against its role in organizing edge dynamics. Finally, using a simple model of actin-myosin network, we show that force-distance relationship might be an emergent feature of such networks. Traction forces are generated by cellular actin-myosin system and transmitted to the environment through adhesions. They are believed to drive cell motion, shape changes, and extracellular matrix remodeling [1Schwarz U.S. Gardel M.L. United we stand: integrating the actin cytoskeleton and cell-matrix adhesions in cellular mechanotransduction.J. Cell Sci. 2012; 125: 3051-3060Crossref PubMed Scopus (256) Google Scholar, 2Polacheck W.J. Chen C.S. Measuring cell-generated forces: a guide to the available tools.Nat. Methods. 2016; 13: 415-423Crossref PubMed Scopus (291) Google Scholar, 3Nerger B.A. Siedlik M.J. Nelson C.M. Microfabricated tissues for investigating traction forces involved in cell migration and tissue morphogenesis.Cell. Mol. Life Sci. 2017; 74: 1819-1834Crossref PubMed Scopus (14) Google Scholar]. However, most of the traction force analysis has been performed on stationary cells, investigating forces at the level of individual focal adhesions or linking them to static cell parameters, such as area and edge curvature [4Aratyn-Schaus Y. Gardel M.L. Transient frictional slip between integrin and the ECM in focal adhesions under myosin II tension.Curr. Biol. 2010; 20: 1145-1153Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 5Rape A.D. Guo W.H. Wang Y.L. The regulation of traction force in relation to cell shape and focal adhesions.Biomaterials. 2011; 32: 2043-2051Crossref PubMed Scopus (222) Google Scholar, 6Oakes P.W. Banerjee S. Marchetti M.C. Gardel M.L. Geometry regulates traction stresses in adherent cells.Biophys. J. 2014; 107: 825-833Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar, 7Murrell M. Oakes P.W. Lenz M. Gardel M.L. Forcing cells into shape: the mechanics of actomyosin contractility.Nat. Rev. Mol. Cell Biol. 2015; 16: 486-498Crossref PubMed Scopus (331) Google Scholar, 8Kassianidou E. Brand C.A. Schwarz U.S. Kumar S. Geometry and network connectivity govern the mechanics of stress fibers.Proc. Natl. Acad. Sci. USA. 2017; 114: 2622-2627Crossref PubMed Scopus (34) Google Scholar, 9Wu Z. Plotnikov S.V. Moalim A.Y. Waterman C.M. Liu J. Two distinct actin networks mediate traction oscillations to confer focal adhesion mechanosensing.Biophys. J. 2017; 112: 780-794Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 10Vianay B. Senger F. Alamos S. Anjur-Dietrich M. Bearce E. Cheeseman B. Lee L. Théry M. Variation in traction forces during cell cycle progression.Biol. Cell. 2018; 110: 91-96Crossref PubMed Scopus (33) Google Scholar]. It is not well understood how traction forces are related to shape changes and motion, e.g., forces were reported to either increase or drop prior to cell retraction [11Doyle A. Marganski W. Lee J. Calcium transients induce spatially coordinated increases in traction force during the movement of fish keratocytes.J. Cell Sci. 2004; 117: 2203-2214Crossref PubMed Scopus (62) Google Scholar, 12Lombardi M.L. Knecht D.A. Dembo M. Lee J. Traction force microscopy in Dictyostelium reveals distinct roles for myosin II motor and actin-crosslinking activity in polarized cell movement.J. Cell Sci. 2007; 120: 1624-1634Crossref PubMed Scopus (82) Google Scholar, 13Ji L. Lim J. Danuser G. Fluctuations of intracellular forces during cell protrusion.Nat. Cell Biol. 2008; 10: 1393-1400Crossref PubMed Scopus (142) Google Scholar, 14Tanimoto H. Sano M. A simple force-motion relation for migrating cells revealed by multipole analysis of traction stress.Biophys. J. 2014; 106: 16-25Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 15Barnhart E. Lee K.C. Allen G.M. Theriot J.A. Mogilner A. Balance between cell-substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes.Proc. Natl. Acad. Sci. USA. 2015; 112: 5045-5050Crossref PubMed Scopus (71) Google Scholar]. Here, we analyze the dynamics of traction forces during the protrusion-retraction cycle of polarizing fish epidermal keratocytes and find that forces fluctuate together with the cycle, increasing during protrusion and reaching maximum at the beginning of retraction. We relate force dynamics to the recently discovered phenomenological rule [16Raynaud F. Ambühl M.E. Gabella C. Bornert A. Sbalzarini I.F. Meister J.-J. Verkhovsky A.B. Minimal model for spontaneous cell polarization and edge activity in oscillating, rotating and migrating cells.Nat. Phys. 2016; 12: 367-373Crossref Scopus (23) Google Scholar] that governs cell-edge behavior during keratocyte polarization: both traction forces and probability of switch from protrusion to retraction increase with the distance from the cell center. Diminishing forces with cell contractility inhibitor leads to decreased edge fluctuations and abnormal polarization, although externally applied force can induce protrusion-retraction switch. These results suggest that forces mediate distance sensitivity of the edge dynamics and organize cell-edge behavior, leading to spontaneous polarization. Actin flow rate did not exhibit the same distance dependence as traction stress, arguing against its role in organizing edge dynamics. Finally, using a simple model of actin-myosin network, we show that force-distance relationship might be an emergent feature of such networks. Uncovering the mutual relationship between adhesion, traction forces, and cell shape is important to understand cell-shape changes and motion [11Doyle A. Marganski W. Lee J. Calcium transients induce spatially coordinated increases in traction force during the movement of fish keratocytes.J. Cell Sci. 2004; 117: 2203-2214Crossref PubMed Scopus (62) Google Scholar, 12Lombardi M.L. Knecht D.A. Dembo M. Lee J. Traction force microscopy in Dictyostelium reveals distinct roles for myosin II motor and actin-crosslinking activity in polarized cell movement.J. Cell Sci. 2007; 120: 1624-1634Crossref PubMed Scopus (82) Google Scholar, 14Tanimoto H. Sano M. A simple force-motion relation for migrating cells revealed by multipole analysis of traction stress.Biophys. J. 2014; 106: 16-25Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 15Barnhart E. Lee K.C. Allen G.M. Theriot J.A. Mogilner A. Balance between cell-substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes.Proc. Natl. Acad. Sci. USA. 2015; 112: 5045-5050Crossref PubMed Scopus (71) Google Scholar, 17Keren K. Pincus Z. Allen G.M. Barnhart E.L. Marriott G. Mogilner A. Theriot J.A. Mechanism of shape determination in motile cells.Nature. 2008; 453: 475-480Crossref PubMed Scopus (528) Google Scholar, 18Barnhart E.L. Lee K.C. Keren K. Mogilner A. Theriot J.A. An adhesion-dependent switch between mechanisms that determine motile cell shape.PLoS Biol. 2011; 9: e1001059Crossref PubMed Scopus (214) Google Scholar, 19Guetta-Terrier C. Monzo P. Zhu J. Long H. Venkatraman L. Zhou Y. Wang P. Chew S.Y. Mogilner A. Ladoux B. Gauthier N.C. Protrusive waves guide 3D cell migration along nanofibers.J. Cell Biol. 2015; 211: 683-701Crossref PubMed Scopus (50) Google Scholar, 20Yip A.K. Iwasaki K. Ursekar C. Machiyama H. Saxena M. Chen H. Harada I. Chiam K.H. Sawada Y. Cellular response to substrate rigidity is governed by either stress or strain.Biophys. J. 2013; 104: 19-29Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 21Panzetta V. Fusco S. Netti P.A. Cell mechanosensing is regulated by substrate strain energy rather than stiffness.Proc. Natl. Acad. Sci. USA. 2019; 116: 22004-22013Crossref PubMed Scopus (38) Google Scholar, 22Giannone G. Dubin-Thaler B.J. Döbereiner H.G. Kieffer N. Bresnick A.R. Sheetz M.P. Periodic lamellipodial contractions correlate with rearward actin waves.Cell. 2004; 116: 431-443Abstract Full Text Full Text PDF PubMed Scopus (470) Google Scholar, 23Burnette D.T. Manley S. Sengupta P. Sougrat R. Davidson M.W. Kachar B. Lippincott-Schwartz J. A role for actin arcs in the leading-edge advance of migrating cells.Nat. Cell Biol. 2011; 13: 371-381Crossref PubMed Scopus (262) Google Scholar, 24Monzo P. Chong Y.K. Guetta-Terrier C. Krishnasamy A. Sathe S.R. Yim E.K.F. Ng W.H. Ang B.T. Tang C. Ladoux B. et al.Mechanical confinement triggers glioma linear migration dependent on formin FHOD3.Mol. Biol. Cell. 2016; 27: 1246-1261Crossref PubMed Scopus (41) Google Scholar]. In a model system of migrating fish epidermal keratocytes, it is relatively well understood how actin assembly, adhesion, and contractile forces determine the regular shape of polarized cells [17Keren K. Pincus Z. Allen G.M. Barnhart E.L. Marriott G. Mogilner A. Theriot J.A. Mechanism of shape determination in motile cells.Nature. 2008; 453: 475-480Crossref PubMed Scopus (528) Google Scholar, 18Barnhart E.L. Lee K.C. Keren K. Mogilner A. Theriot J.A. An adhesion-dependent switch between mechanisms that determine motile cell shape.PLoS Biol. 2011; 9: e1001059Crossref PubMed Scopus (214) Google Scholar], but much less is known about what happens when the cells actively change their shape. In order to investigate traction force dynamics during keratocyte shape fluctuations and polarization, we plated cells on compliant polyacrylamide (PAA) substrates. In our recent study, we described how local protrusion-retraction fluctuations in fish epidermal keratocytes lead to overall cell polarization [16Raynaud F. Ambühl M.E. Gabella C. Bornert A. Sbalzarini I.F. Meister J.-J. Verkhovsky A.B. Minimal model for spontaneous cell polarization and edge activity in oscillating, rotating and migrating cells.Nat. Phys. 2016; 12: 367-373Crossref Scopus (23) Google Scholar]. We uncovered a phenomenological rule that governs these dynamics: transitions from protrusion to retraction preferentially happen at a certain threshold distance from the cell center. This distance-sensing rule implemented in a stochastic model was sufficient to reproduce the emergence of polarized state and directional motion from apparently disorganized protrusion-retraction fluctuations. We tested whether the cells on PAA substrates exhibited the same behavior as we have previously observed on rigid glass substrates. On very soft PAA (3KPa), keratocytes initially spread to a much smaller area than on glass, exhibited only small shape fluctuations, and polarized very rapidly. However, increasing PAA elastic modulus to 16KPa yielded the behavior that was indistinguishable from the one observed on glass: cells spread and exhibited large protrusion-retraction fluctuations and apparent waves traveling around the cell perimeter, eventually consolidating in one protruding front and one retracting back (Figure 1A; Video S1). In order to have sufficiently large time and space window to observe polarization process, we have selected PAA with elastic modulus of 16KPa for all subsequent experiments. https://www.cell.com/cms/asset/1f6ea39e-e63a-4b5c-a7fd-8b9231618a7a/mmc2.mp4Loading ... Download .mp4 (12.29 MB) Help with .mp4 files Video S1. Cell Fluctuating before Polarization, Related to Figure 1Face to face images of TFM (left) and phase contrast (right) of a cell before polarization. Scalebar, 20μm. Physical mechanism of how the cell controls the distribution of protrusion-retraction transitions is not known. Here, we investigate traction force dynamics during polarization to test the hypothesis that traction force could be the mediator of distance sensing and a trigger for protrusion-retraction switches. Traction force microscopy of polarizing cells revealed a very dynamic stress distribution (Figure 1A; Video S1). At all stages of polarization, traction forces were oriented generally radially toward the cell center. At the onset of spreading, the region of high stress formed an almost continuous ring at the cell periphery, but then the ring broke in the multiple foci, which moved, appeared, disappeared, fused, and split but generally always followed the tips of extending regions of the cell. When the cells eventually polarized and started to move persistently, stress foci localized to the two lateral cell extremities (Figure 1A) (580s), as previously reported [25Oliver T. Dembo M. Jacobson K. Separation of propulsive and adhesive traction stresses in locomoting keratocytes.J. Cell Biol. 1999; 145: 589-604Crossref PubMed Scopus (140) Google Scholar, 26Fournier M.F. Sauser R. Ambrosi D. Meister J.J. Verkhovsky A.B. Force transmission in migrating cells.J. Cell Biol. 2010; 188: 287-297Crossref PubMed Scopus (180) Google Scholar]. Thus, both during and after polarization, stresses were found in the regions of the cell that were most distant from the cell center. Visualizing force foci simultaneously with the regions of protrusion-retraction switches (defined in the substrate frame as described in [16Raynaud F. Ambühl M.E. Gabella C. Bornert A. Sbalzarini I.F. Meister J.-J. Verkhovsky A.B. Minimal model for spontaneous cell polarization and edge activity in oscillating, rotating and migrating cells.Nat. Phys. 2016; 12: 367-373Crossref Scopus (23) Google Scholar]; see also STAR Methods) in the video sequences revealed a close proximity and a coordinated movement of switch sites and force foci (Figure 1C; Video S2). Note that protrusion-retraction switches mapped directly to the cells edge, although the centers of the force foci localized inside the cell perimeter at a small distance from the edge, so there was no direct colocalization between the two. Nevertheless, proximity between the switches and force foci was apparent visually and also revealed by plotting the distribution of their separating distances. This distribution peaked at 5 μm, which is comparable to the width of the lamellipodia, suggesting that force foci were localized at focal adhesions at its base (Figure S1A). More evidence for the coordination between edge dynamics and the stress emerged from the comparison of the time evolutions of edge position and stress along the same radial line (Figure 1C, kymograph). In multiple cycles of protrusion and retraction, force spot followed the edge, moving outward and increasing in intensity during protrusion and shifting inward and diminishing during retraction. Taken together, these observations are consistent with the idea that the increase of inward-oriented traction forces during protrusion leads to eventual switch to retraction, which might be powered by the same forces. https://www.cell.com/cms/asset/f5e3600b-a35f-46ce-9b16-777c4161fb81/mmc3.mp4Loading ... Download .mp4 (2.79 MB) Help with .mp4 files Video S2. Stress Foci Colocalize with Switches from Protrusion to Retraction in Fluctuating Cell, Related to Figure 1Cell outline is in dark green, switches are in black, stress is color coded. Treatment of the cells with contractility inhibitor blebbistatin prior to polarization dramatically reduced not only traction forces but also the dynamics. Treated cells exhibited only very small protrusion-retraction fluctuations (Figure 1B). They eventually started to move but did not keep a stable crescent shape, instead either extending uncontrollably in width or splitting into fragments (Video S3). Such behavior was observed in other cell types and also predicted theoretically [27Cai Y. Rossier O. Gauthier N.C. Biais N. Fardin M.A. Zhang X. Miller L.W. Ladoux B. Cornish V.W. Sheetz M.P. Cytoskeletal coherence requires myosin-IIA contractility.J. Cell Sci. 2010; 123: 413-423Crossref PubMed Scopus (155) Google Scholar, 28Kabaso D. Shlomovitz R. Schloen K. Stradal T. Gov N.S. Theoretical model for cellular shapes driven by protrusive and adhesive forces.PLoS Comput. Biol. 2011; 7: e1001127Crossref PubMed Scopus (46) Google Scholar]. It points to the importance of the traction forces to the ability of the cell to control their size and to retract its edge properly. Finally, application of the external force on a blebbistatin-treated cell by pulling on the compliant substrate with a micropipette induced dramatic edge retraction and eventual polarization (Video S4). These observations suggest together a possible causal relationship between traction stress and edge retraction. https://www.cell.com/cms/asset/f16592a3-20a5-4cde-a8e9-89a565cb32ff/mmc4.mp4Loading ... Download .mp4 (3.63 MB) Help with .mp4 files Video S3. Cells Treated with Blebbistatin Split upon Polarization, Related to Figure 1Phase constrast image sequence of cells treated with 100μM of contractility inhibitor blebbistatin. Bright debris are blebbistatin precipitates. The solution is practically saturated. Scalebar, 30μm. https://www.cell.com/cms/asset/9bc85e75-8afb-4971-b0f6-acc0b0d88f1a/mmc5.mp4Loading ... Download .mp4 (10.1 MB) Help with .mp4 files Video S4. Externally Applied Force on a Blebbistatin-Treated Cell Induces Dramatic Edge Retraction, Related to Figure 1Force is applied to a cell treated with 100μM of contractility inhibitor blebbistatin by pulling on the compliant substrate with a micropipette. Bright debris are blebbistatin precipitates. The solution is practically saturated. Scalebar, 30μm. In our recent study, we have established that protrusion-retraction switches happen preferentially at the longest distance from the geometrical cell center. If these switches are indeed triggered by the increase in traction force, one should expect that traction forces increase with the distance from the cell center. We have plotted local stresses within the cell area versus distances from the cell center to the locations where these stresses were measured (see STAR Methods). Figure 2A demonstrates a strong positive correlation between the normalized stress and the normalized distance (Spearman’s rank correlation coefficient ρS=0.67). Normalization allowed aggregating the data from long sequences of multiple cells. Non-normalized stress-distance relationships revealed that maximal center-to-edge distance tended to increase with time during polarization process, although the local stress tended to decrease. Nevertheless, positive correlation between the non-normalized values of stress and distance was always evident when considering relatively short time intervals, including parts of the sequences after polarization, when the stress foci localized to lateral cell extremities (Figure S2B). To get more insight into force-distance relationship, we compared maximal center-to-edge distances and stresses in the cells under different conditions: on substrates of various rigidities and under the influence of drugs modifying myosin contractility and actin polymerization (Figure 2B). As the majority of protrusion-retraction switches happen at the maximal distances from the center to the edge, the maximal center-to-edge distance is a measure of switching distance. On soft substrates, the cells exhibited lower maximal extensions and lower traction stresses than on rigid substrates. This is consistent with previous findings about adhesion reinforcement by substrate rigidity [20Yip A.K. Iwasaki K. Ursekar C. Machiyama H. Saxena M. Chen H. Harada I. Chiam K.H. Sawada Y. Cellular response to substrate rigidity is governed by either stress or strain.Biophys. J. 2013; 104: 19-29Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 21Panzetta V. Fusco S. Netti P.A. Cell mechanosensing is regulated by substrate strain energy rather than stiffness.Proc. Natl. Acad. Sci. USA. 2019; 116: 22004-22013Crossref PubMed Scopus (38) Google Scholar]. Contractility activator calyculin A and low doses of actin polymerization inhibitor cytochalasin D both induced cells to retract, which was accompanied by a decrease in traction stress. As already mentioned, inhibitor of myosin activity blebbistatin induced dramatic decrease in traction stress. This was accompanied by a change in the distribution of maximal cell extension: the cells generally extended and fluctuated less than in control before polarization but extended much more once polarized. This is reflected in the asymmetric extension distribution with large number of very high extension values (Figure 2B). These results suggest that cell extension and traction stresses are controlled by multiple factors involving the balance of adhesion strength, actin protrusion, and contractility. For example, decrease in cell extension and traction stress in the presence of calyculin could be explained by increase of contractility without matching increase in adhesion so that enhanced cytoskeletal contraction led to retraction but did not result in increased traction at the substrate level. Importantly, in all conditions except blebbistatin treatment, the changes in cell extension were matched by parallel changes in traction stresses. Thus, under different conditions, cells retracted at different distances and at different stress values, but the stress-distance relationship was largely preserved through variety of conditions. Correlation between maximal stress and the longest cell dimension was previously reported in a study using stationary cells and patterned substrates to allow precise control over the cell shape [5Rape A.D. Guo W.H. Wang Y.L. The regulation of traction force in relation to cell shape and focal adhesions.Biomaterials. 2011; 32: 2043-2051Crossref PubMed Scopus (222) Google Scholar]. Another study employing cell shape patterning suggested that the overall magnitude of the traction forces depends on the cell spread area, although their local values are defined by the curvature of the cell edge [6Oakes P.W. Banerjee S. Marchetti M.C. Gardel M.L. Geometry regulates traction stresses in adherent cells.Biophys. J. 2014; 107: 825-833Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar]. However, in polarizing keratocytes, we did not observe a correlation between the stress and local edge curvature (Figure S2A) (ρS=0.11). Interestingly, the behavior of protrusion-retraction switches in this respect paralleled the behavior of stress: switches were enriched at high distances from the cell center, but not enriched at high edge curvature (Figure S1B). To get more insight into the relationship between traction stress and edge dynamics, we investigated how stress and cell edge position changed with time. Because we were specifically interested in protrusion-retraction events, we identified many such events and measured the stress and edge velocity around the time of these events (see STAR Methods). At the onset of protrusion, stress was low and protrusion rate was high. With the extent of protrusion, its rate gradually decreased while the stress increased continuously during protrusion and also for a few seconds after the onset of retraction, decreasing rapidly thereafter (Figure 2C). Interestingly, the maximum of retraction velocity was also observed shortly after the onset of retraction, coinciding in time with the stress maximum. This coincidence might indicate that the origin of this high stress was viscous friction between retracting cell structures and the extracellular matrix [29Bangasser B.L. Rosenfeld S.S. Odde D.J. Determinants of maximal force transmission in a motor-clutch model of cell traction in a compliant microenvironment.Biophys. J. 2013; 105: 581-592Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar]. Complementary analysis of the relationship between stress and edge dynamics is provided by measuring the correlation between the change of stress and the edge velocity. Change of stress was measured between two consecutive frames. Velocity was determined from the change of edge position between two frames. We measured the time correlation function of stress and velocity, i.e., how the correlation between the change of stress and edge velocity depended on the time interval between the two measurements (see STAR Methods). The highest correlation was observed when the velocity measurement was shifted between 10 and 20s backward with respect to the stress measurement (Figure 2D). In other words, when the s" @default.
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• W3013611737 title "Traction Forces Control Cell-Edge Dynamics and Mediate Distance Sensitivity during Cell Polarization" @default.
• W3013611737 cites W1587940648 @default.
• W3013611737 cites W1969011037 @default.
• W3013611737 cites W1979984413 @default.
• W3013611737 cites W1980861723 @default.
• W3013611737 cites W1987139499 @default.
• W3013611737 cites W2003599204 @default.
• W3013611737 cites W2004374176 @default.
• W3013611737 cites W2005809817 @default.
• W3013611737 cites W2008063578 @default.
• W3013611737 cites W2024438127 @default.
• W3013611737 cites W2027411306 @default.
• W3013611737 cites W2036071626 @default.
• W3013611737 cites W2038870603 @default.
• W3013611737 cites W2047253804 @default.
• W3013611737 cites W2047903964 @default.
• W3013611737 cites W2052485377 @default.
• W3013611737 cites W2058658516 @default.
• W3013611737 cites W2060432794 @default.
• W3013611737 cites W2083748759 @default.
• W3013611737 cites W2095625881 @default.
• W3013611737 cites W2100324155 @default.
• W3013611737 cites W2103495097 @default.
• W3013611737 cites W2107750328 @default.
• W3013611737 cites W2114589293 @default.
• W3013611737 cites W2120795306 @default.
• W3013611737 cites W2132104128 @default.
• W3013611737 cites W2135165925 @default.
• W3013611737 cites W2148606469 @default.
• W3013611737 cites W2150338395 @default.
• W3013611737 cites W2159430493 @default.
• W3013611737 cites W2261738812 @default.
• W3013611737 cites W2305154056 @default.
• W3013611737 cites W2345307871 @default.
• W3013611737 cites W2347034616 @default.
• W3013611737 cites W2397027267 @default.
• W3013611737 cites W2567098509 @default.
• W3013611737 cites W2588908786 @default.
• W3013611737 cites W2592965097 @default.
• W3013611737 cites W2943127305 @default.
• W3013611737 cites W2953382198 @default.
• W3013611737 cites W2977831657 @default.
• W3013611737 cites W3103145119 @default.
• W3013611737 cites W413440677 @default.
• W3013611737 cites W982799556 @default.
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