Criticality of plasma membrane lipids reflects activation state of macrophage cells

Cammarota, Eugenia; Soriani, Chiara; Taub, Raphaelle; Morgan, Fiona J. E.; Sakai, Jiro; Veatch, Sarah L.; Bryant, Clare E.; Cicuta, Pietro

doi:10.1101/680157

Cited by 5 publications

(8 citation statements)

References 59 publications

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“…A possible explanation came in 2008 when it was shown that freshly isolated GPMVs exhibited hallmarks of criticality, placing them close to a room temperature miscibility critical point (81). Over time, additional studies have documented how GPMV phase behavior is impacted by growth conditions in cells (82)(83)(84) and differentiation into other cell types (85,86), and lipidomics analysis has begun to characterize the vast compositional complexity of these membranes (82,84,87).…”

Section: Isolated Membranesmentioning

confidence: 99%

Critical Phenomena in Plasma Membrane Organization and Function

Shaw

Ghosh

Veatch

2021

Annu. Rev. Phys. Chem.

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Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support for the notion that lipid organization plays an important role in modulating this heterogeneity. Various biophysical mechanisms rooted in the concept of liquid–liquid phase separation have been proposed to explain diverse experimental observations of heterogeneity in model and cell membranes with distinct but overlapping applicability. In this review, we focus on the evidence for and the consequences of the hypothesis that the plasma membrane is poised near an equilibrium miscibility critical point. Critical phenomena explain certain features of the heterogeneity observed in cells and model systems but also go beyond heterogeneity to predict other interesting phenomena, including responses to perturbations in membrane composition. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 72 is April 20, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Isolated Membranesmentioning

confidence: 99%

Critical Phenomena in Plasma Membrane Organization and Function

Shaw

Ghosh

Veatch

2021

Annu. Rev. Phys. Chem.

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“…Cultures at 20°C grow at a slower rate and therefore were started at a higher concentration to reach the same optical density (a proxy for growth stage) in an equivalent amount of time. We prioritized cell density because it has been shown to influence transition temperatures in cell-derived membranes (25, 26). Incubator temperature was monitored with a Fisherbrand TraceableLIVE Wi-Fi Datalogging Thermometer (0.25°C accuracy).…”

Section: Methodsmentioning

confidence: 99%

“…It is reasonable to expect that yeast should actively remodel their vacuole membranes to achieve phase separation, because domains appear and disappear with growth stage and because yeast adjust to a wide range of environmental conditions (18,19) . More broadly, it is known that many cell types alter their lipid compositions and membrane behaviors in response to changes in cell cycle (20)(21)(22)(23)(24)(25) , activation (26,27) , disease (28)(29)(30) , and environmental stress (31) . Changes in growth temperature are particularly compelling to investigate because they are experimentally tractable and because they trigger active membrane remodeling in organisms ranging from bacteria to vertebrate animals (32)(33)(34)(35) .…”

Section: Introductionmentioning

confidence: 99%

Yeast cells actively tune their membranes to phase separate at temperatures that scale with growth temperatures

Leveille

Cornell

Keller

2021

Preprint

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Membranes of vacuoles, the lysosomal organelles in yeast, undergo extraordinary changes during the cell's normal growth cycle. The cycle begins with a stage of rapid cell growth. Then, as glucose becomes scarce, growth slows, and the vacuole membranes phase-separate into micron-scale liquid domains. Recent studies suggest that these domains are important for yeast survival by laterally organizing membrane proteins that play a key role in a central signaling pathway conserved among eukaryotes (TORC1). An outstanding question in the field has been whether yeast stringently regulate the phase transition and how they respond to new physical conditions. Here, we measure transition temperatures - an increase of roughly 15°C returns vacuole membranes to a state that appears uniform across a range of growth temperatures. We find that broad populations of yeast grown at a single temperature regulate the transition to occur over a surprisingly narrow temperature range. Moreover, the transition temperature scales linearly with the growth temperature, demonstrating that the cells physiologically adapt to maintain proximity to the transition. Next, we ask how yeast adjust their membranes to achieve phase separation. Specifically, we test how levels of ergosterol, the main sterol in yeast, induce or eliminate membrane domains. We isolate vacuoles from yeast during their rapid stage of growth, when their membranes do not natively exhibit domains. We find that membrane domains materialize when ergosterol is depleted, contradicting the assumption that increases in ergosterol cause membrane phase separation in vivo, and in agreement with prior studies that use artificial and cell-derived membranes.

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“…Thermodynamic parameters of the membrane still play an important role by tuning the magnitude of membrane phasemediated interactions, changing the composition of domains and modulating interactions between membrane components (Machta et al, 2012). In isolated vesicles, numerous factors impact the location of the macroscopic phase boundary, including cell type, perturbations to lipid homeostasis, incorporation of drugs, and the presence or loss of leaflet asymmetry (Cammarota et al, 2020;Levental et al, 2017Levental et al, , 2020b Instantaneous snapshot of a heterogeneous membrane containing protein structures of increasing complexity, including cortical actin, clustered receptors, adaptor proteins, and membrane proximal signaling assemblies. This membrane contains numerous domains of different sizes and shapes, some of which surround protein rich structures.…”

Section: A New Perspective On Ordered Domains In Cell Membranesmentioning

confidence: 99%

“…While phase separation has emerged as a likely mechanism underlying functional heterogeneity in cell membranes (Eggeling et al, 2009; Koyama-Honda et al, 2020; Sanchez et al, 2012; Sengupta et al, 2007), it is clear that macroscopic phase separation does not occur, and models used to rationalize rafts as phase separated domains either lack utility or are easily disproved, leading to valid skepticism (Kenworthy, 2008; Kraft, 2013; Munro, 2003). In contrast, plasma membranes isolated from cells clearly separate into coexisting liquid-ordered (Lo) and liquid-disordered (Ld) phases (Baumgart et al, 2007), there is clear evidence that membrane composition is carefully tuned and actively maintained by the cell (Ernst et al, 2016; Sviridov and Miller, 2020), and there are examples where this biological tuning impacts the membrane phase transition (Burns et al, 2017; Cammarota et al, 2020; Levental et al, 2020b). A goal of the current work is to address the disconnect between the apparent importance of the phase transition with abundant observations indicating that the membrane is in a single phase under physiological conditions, drawing from an increasingly sophisticated picture of the thermodynamics of phase separation in membranes (Levental et al, 2020a; Shaw et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Membrane phase separation drives organization at B cell receptor clusters

Shelby

Castello-Serrano

et al. 2021

Preprint

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Isolated plasma membranes separate into two coexisting liquid phases with distinct lipid and protein compositions but live cell plasma membranes do not macroscopically phase separate, leading to questions of whether and how the membrane phase transition contributes to functional heterogeneity in cells. Using quantitative super resolution microscopy we show that B cell receptor signaling platforms are nanoscale domains that quantitatively enrich membrane probes based on probe phase partitioning in isolated plasma membrane vesicles. Phase partitioning in vesicles also predicts relative probe mobility and retention at receptor clusters. The convergence between measurements in live cells and isolated membranes establishes a clear role for the membrane phase transition as an organizing principle in cells. We propose that physical properties fundamental to the membrane phase transition give rise to a plasma membrane that is a highly responsive medium, capable of compartmentalizing cellular processes in response to diverse stimuli.

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Criticality of plasma membrane lipids reflects activation state of macrophage cells

Cited by 5 publications

References 59 publications

Critical Phenomena in Plasma Membrane Organization and Function

Critical Phenomena in Plasma Membrane Organization and Function

Yeast cells actively tune their membranes to phase separate at temperatures that scale with growth temperatures

Membrane phase separation drives organization at B cell receptor clusters

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