Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics

Saha, Suvrajit; Nagy, Tamas L.; Weiner, Orion D.

doi:10.1098/rstb.2017.0145

Cited by 57 publications

(52 citation statements)

References 89 publications

(148 reference statements)

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“…Fluorescently tagged transmembrane proteins typically diffuse freely in both artificial bilayers and in intact cells, albeit with a 10-100 fold lower diffusion coefficient in cells (Kusumi et al, 2005). Together these results, each consistent with the fluid mosaic model (Singer and Nicolson, 1972), led to the widespread belief that two-dimensional (2D) flow of lipids in cells mediates rapid intracellular equilibration of membrane tension (Basu et al, 2016; Diz-Muñoz et al, 2013; Fogelson and Mogilner, 2014; Gauthier et al, 2012; Gauthier et al, 2011; Houk et al, 2012; Huse, 2017; Keren et al, 2008; Keren, 2011; Kozlov and Mogilner, 2007; Lieber et al, 2015; Morris and Homann, 2001; Mueller et al, 2017; Mueller et al, 2017; Ofer et al, 2011; Pontes et al, 2017; Saha et al, 2018; Schweitzer et al, 2014; Sens and Plastino, 2015; Watanabe et al, 2013; Winkler et al, 2016), providing a long-range signaling mechanism analogous to the rapid propagation of electrical signals in neurons (Keren, 2011). Some studies have contemplated the possibility of tension gradients in rapidly migrating cells (Basu et al, 2016; Fogelson and Mogilner, 2014; Lieber et al, 2015; Schweitzer et al, 2014), but in these studies the role of membrane-cytoskeleton friction was assumed to be a modest perturbation on the essentially fluid nature of the membrane.…”

Section: Introductionsupporting

confidence: 64%

“…Most studies have assumed that membrane tension is homogeneous across a cell (Basu et al, 2016; Diz-Muñoz et al, 2013; Fogelson and Mogilner, 2014; Gauthier et al, 2012; Gauthier et al, 2011; Houk et al, 2012; Huse, 2017; Keren et al, 2008; Keren, 2011; Kozlov and Mogilner, 2007; Lieber et al, 2015; Morris and Homann, 2001; Mueller et al, 2017; Mueller et al, 2017; Ofer et al, 2011; Pontes et al, 2017; Saha et al, 2018; Schweitzer et al, 2014; Sens and Plastino, 2015; Watanabe et al, 2013; Winkler et al, 2016). This assumption was justified either by analogy to isolated lipid bilayers (Keren et al, 2008; Watanabe et al, 2013), or by reference to experiments where membrane tension was globally perturbed via osmotic shocks or drug addition (Gauthier et al, 2011; Houk et al, 2012; Mueller et al, 2017; Raucher and Sheetz, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Thus it is plausible that cell membranes, too, could exist in a state that behaves as a 2D fluid on the nanoscale but that is closer to a semi-solid gel on the cellular scale. The 2D-gel hypothesis is incompatible with the many conjectures in the literature that rapid propagation of membrane tension can mediate long-range intracellular signaling (Basu et al, 2016; Diz-Muñoz et al, 2013; Fogelson and Mogilner, 2014; Gauthier et al, 2012; Gauthier et al, 2011; Houk et al, 2012; Huse, 2017; Keren et al, 2008; Keren, 2011; Kozlov and Mogilner, 2007; Lieber et al, 2015; Morris and Homann, 2001; Mueller et al, 2017; Mueller et al, 2017; Ofer et al, 2011; Pontes et al, 2017; Saha et al, 2018; Schweitzer et al, 2014; Sens and Plastino, 2015; Watanabe et al, 2013; Winkler et al, 2016). …”

Section: Introductionmentioning

confidence: 94%

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Cell Membranes Resist Flow

Shi

Graber

Baumgart

et al. 2018

Cell

304

292

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SUMMARY The fluid-mosaic model posits a liquid-like plasma membrane, which can flow in response to tension gradients. It is widely assumed that membrane flow transmits local changes in membrane tension across the cell in milliseconds, mediating long-range signaling. Here we show that propagation of membrane tension occurs quickly in cell-attached blebs, but is largely suppressed in intact cells. The failure of tension to propagate in cells is explained by a fluid dynamical model that incorporates the flow resistance from cytoskeleton-bound transmembrane proteins. Perturbations to tension propagate diffusively, with a diffusion coefficient Dσ ~ 0.024 μm2/s in HeLa cells. In primary endothelial cells, local increases in membrane tension lead only to local activation of mechanosensitive ion channels and to local vesicle fusion. Thus membrane tension is not a mediator of long-range intra-cellular signaling, but local variations in tension mediate distinct processes in sub-cellular domains.

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Section: Introductionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

See 1 more Smart Citation

Cell Membranes Resist Flow

Shi

Graber

Baumgart

et al. 2018

Cell

304

292

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“…knockout of HEM1 or ARP2) with mechanical perturbations (to generate long-range negative feedback) that we were able to isolate and dissect the role of branched actin assembly in providing short-range positive feedback. This combined approach revealed that branched actin assembly is not required for short-range positive feedback, in contrast to the general assumptions in the field (Iglesias and Devreotes, 2012;Krause and Gautreau, 2014;Saha et al, 2018;Stanley et al, 2014).…”

Section: Discussionmentioning

confidence: 81%

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

Graziano¹,

Town²,

Nagy³

et al. 2018

Preprint

Self Cite

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Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted Arp2/3 and WAVE complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments.to produce a single protrusion ( Fig. 1A) (Diz-Muñoz et al., 2016;Houk et al., 2012;Keren et al., 2008;Sens and Plastino, 2015).While actin polymerization serves as a key ingredient in generating the positive and negative feedback loops that give rise to polarity, we lack an understanding of how specific types of actin networks provide each kind of feedback. Immune cells assemble multiple actin networks at different subcellular locations that carry out distinct functions to support migration: Arp2/3dependent assembly of branched actin networks at the leading edge contributes to cell guidance/steering and protrusion extension, while actomyosin bundles near the trailing edge provide contractile force to lift the cell rear and squeeze the cell body forward (Lämmermann and Germain, 2014;Moreau et al., 2018). Along with these functional differences, the types of actin networks immune cells and other migratory cells employ for migration vary with microenvironment (Lämmermann and Germain, 2014;Paluch et al., 2016). The role of actin dynamics in migration is complex and likely depends on the type of actin network, its subcellular location, and the extracellular environment. Existing tools to probe the role of actin networks in both the positive and negative feedback loops needed for polarity are fairly crude and have largely been based on pharmacological perturbations that target all actin polymer (Diz-Muñoz et al., 2016;Huang et al., 2013;Inoue and Meyer, 2008;Sasaki et al., 2007;Wang et al., 2002;Weiner et al., 2007;Yang et al., 2016). More surgical experiments are needed to clarify how different subcellular actin networks contribute to polarity generation under different environmental conditions. Figure 1. WAVE complex is required for neutrophil polarity and motility.A) Polarity generation depends on fast-acting, short-range positive feedback and slower-acting, long-range negative feedback. Actin assembly participates in both types of feedback, with its role in negat...

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“…Another example of such direct connection between physics and biology can be found in the crosstalk between physical forces and biochemical signalling, as described in the paper by Weiner and co-workers [12]. They review the self-organization of actin polymerization and acto-myosin contractility in the context of migration, where membrane tension is an important player.…”

mentioning

confidence: 99%