Critical Phenomena in Plasma Membrane Organization and Function

Shaw, Thomas R.; Ghosh, Subhadip; Veatch, Sarah L.

doi:10.1146/annurev-physchem-090419-115951

Cited by 51 publications

(52 citation statements)

References 167 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, by demonstrating lipid liquid-gel phase separation and the associated membrane protein segregation occurring in protein-crowded, native membranes of living cells, our results are fully consistent with comparable phenomena observed in simplified in vitro and in silico model systems (Domanski et al , 2012; Picas et al , 2010; Suárez-Germà et al , 2011; Shaw et al , 2021), thus providing strong, complementary in vivo support for the general validity of the respective membrane models.…”

Section: Discussionsupporting

confidence: 82%

“…Finally, lipid phases can co-exist, resulting in separated membrane areas exhibiting distinctly different composition and characteristics (Baumgart et al , 2007; Nickels et al , 2017; Elson et al , 2010; Heberle & Feigenson, 2011; Shen et al , 2017). This principal mechanism of lipid domain formation is best studied in the context of lipid rafts (Lingwood & Simons, 2010; Shaw et al , 2021). Here the co-existence of fluid liquid-disordered and liquid-ordered phases, and the associated protein segregation, has been demonstrated in membranes of living eukaryotic cells (Toulmay & Prinz, 2013; Shelby et al , 2021).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low membrane fluidity triggers lipid phase separation and protein segregation in vivo

Gohrbandt

Lipski

Grimshaw

et al. 2019

Preprint

View full text Add to dashboard Cite

Important physicochemical properties of cell membranes such as fluidity sensitively depend on fluctuating environmental factors including temperature, pH or diet. To counteract these disturbances, living cells universally adapt their lipid composition in return. In contrast to eukaryotic cells, bacteria tolerate surprisingly drastic changes in their lipid composition while retaining viability, thus making them a more tractable model to study this process. Using the model organisms Escherichia coli and Bacillus subtilis, which regulate their membrane fluidity with different fatty acid types, we show here that inadequate membrane fluidity interferes with essential cellular processes such as morphogenesis and maintenance of membrane potential, and triggers large-scale lipid phase separation that drives protein segregation into the fluid phase. These findings illustrate why lipid homeostasis is such a critical cellular process. Finally, our results provide direct in vivo support for current in vitro and in silico models regarding lipid phase separation and associated protein segregation.Keywords: Lipid phase separation, lipid domains, protein partitioning, membrane fluidity, homeoviscous adaptation, Escherichia coli, Bacillus subtilis, WALP, FOF1 ATP synthase liquid-disordered phase characterized by low packing density and high diffusion rates that forms the regular state of biological membranes, (ii) the more ordered, cholesterol/hopanoid-dependent liquidordered phase found in biological membranes in form of lipid rafts, and (iii) the gel phase characterized by dense lipid packing with little lateral or rotational diffusion, which is generally assumed to be absent in biologically active membranes (Schmid, 2017;Veatch, 2007). In fact, the temperature associated with gel phase formation has been postulated to define the lower end of the temperature range able to support vital cell functions (Burns et al., 2017;Drobnis et al., 1993;Ghetler et al., 2005). At last, the lipid phases can co-exist, resulting in separated membrane areas exhibiting distinctly different composition and characteristics (Baumgart et al., 2007;Elson et al., 2010;Heberle and Feigenson, 2011). This principal mechanism of lipid domain formation is best studied in the context of lipid rafts (Lingwood and Simons, 2010).While in vitro and in silico approaches with simplified lipid models have provided detailed insights into the complex physicochemical behavior of lipid bilayers, testing the formed hypotheses and models in the context of protein-rich biological membranes is now crucial. Bacteria tolerate surprisingly drastic changes in their lipid composition and only possess one or two membrane layers as part of their cell envelope. Consequently, bacteria are both a suitable and a more tractable model to study the fundamental biological process linked to membrane fluidity and phase separation in vivo.We analyzed the biological importance of membrane homeoviscous adaptation in Escherichia coli (phylum Proteobacteria) and Bacillus subtilis (phylum Firmic...

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Low membrane fluidity triggers lipid phase separation and protein segregation in vivo

Gohrbandt

Lipski

Grimshaw

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Lipid-based phase behavior within the plasma membrane is one of the biophysical properties most heavily studied over the last decades [9][10][11] . Early indications from biochemical analyses of detergent-resistant membrane fractions 12 and recent high-resolution spectroscopic [13][14][15][16][17] and super-resolution microscopic [18][19][20][21] measurements are consistent with the presence of nanoscopic phase-like organization in the steady-state plasma membrane of resting and stimulated cells.…”

Section: Phase-like Properties Of Plasma Membanesmentioning

confidence: 99%

Transbilayer Coupling of Lipids in Cells Investigated by Imaging Fluorescence Correlation Spectroscopy

Bag

London

Holowka

et al. 2022

Preprint

View full text Add to dashboard Cite

Plasma membrane hosts numerous receptors, sensors, and ion channels involved in cellular signaling. Phase separation of the plasma membrane is emerging as a key biophysical regulator of signaling reactions in multiple physiological and pathological contexts. There is much evidence that plasma membrane composition supports the co-existence liquid-ordered (Lo) and liquid-disordered (Ld) phases or domains at physiological conditions. However, this phase/domain separation is nanoscopic and transient in live cells. It is recently proposed that transbilayer coupling between the inner and outer leaflets of the plasma membrane is driven by their asymmetric lipid distribution and by dynamic cytoskeleton-lipid composites that contribute to the formation and transience of Lo/Ld phase separation in live cells. In this Perspective, we highlight new approaches to investigate how transbilayer coupling may influence phase separation. For quantitative evaluation of the impact of these interactions, we introduce an experimental strategy centered around Imaging Fluorescence Correlation Spectroscopy (ImFCS), which measures membrane diffusion with very high precision. To demonstrate this strategy we choose two well-established model systems for transbilayer interactions: crosslinking by multivalent antigen of immunoglobulin E bound to receptor FcεRI, and crosslinking by cholera toxin B of GM1 gangliosides. We discuss emerging methods to systematically perturb membrane lipid composition, particularly exchange of outer leaflet lipids with exogenous lipids using methyl alpha cyclodextrin. These selective perturbations may be quantitatively evaluated with ImFCS and other high-resolution biophysical tools to discover novel principles of lipid-mediated phase separation in live cells in the context of their pathophysiological relevance.

show abstract

“…37 Perhaps, the chemical activity of the cholesterol in biological membranes is influenced by the ordering of their lipids or by domain formation. 26,[67][68][69] Or could amphiphiles such as free fatty acids associate with the phospholipids in the EMs in vivo and displace their cholesterol? 70 This would require significant amounts of such a competitor, thus far undetected.…”

Section: The Concentration Of Cholesterol In Typicalmentioning

confidence: 99%

A basic model for cell cholesterol homeostasis

Steck

Tabei

Lange

2021

Traffic

View full text Add to dashboard Cite

Cells manage their cholesterol by negative feedback using a battery of sterol-responsive proteins. How these activities are coordinated so as to specify the abundance and distribution of the sterol is unclear. We present a simple mathematical model that addresses this question. It assumes that almost all of the cholesterol is associated with phospholipids in stoichiometric complexes. A small fraction of the sterol is uncomplexed and thermodynamically active. It equilibrates among the organelles, setting their sterol level according to the affinity of their phospholipids. The activity of the homeostatic proteins in the cytoplasmic membranes is then set by their fractional saturation with uncomplexed cholesterol in competition with the phospholipids. The high-affinity phospholipids in the plasma membrane (PM) are filled to near stoichiometric equivalence, giving it most of the cell sterol. Notably, the affinity of the phospholipids in the endomembranes (EMs) is lower by orders of magnitude than that of the phospholipids in the PM. Thus, the small amount of sterol in the EMs rests far below stoichiometric capacity. Simulations match a variety of experimental data. The model captures the essence of cell cholesterol homeostasis, makes coherent a diverse set of experimental findings, provides a surprising prediction and suggests new experiments.

show abstract

Critical Phenomena in Plasma Membrane Organization and Function

Cited by 51 publications

References 167 publications

Low membrane fluidity triggers lipid phase separation and protein segregation in vivo

Low membrane fluidity triggers lipid phase separation and protein segregation in vivo

Transbilayer Coupling of Lipids in Cells Investigated by Imaging Fluorescence Correlation Spectroscopy

A basic model for cell cholesterol homeostasis

Contact Info

Product

Resources

About