Loss of plasma membrane lipid asymmetry can induce ordered domain (raft) formation

Kakuda, Shinako; Suresh, Pavana; Li, Guangtao; London, Erwin

doi:10.1016/j.jlr.2021.100155

Cited by 12 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Perhaps the native lipid composition of the plasma membrane leaflets in the living cell suppresses EphA2 heterogeneities. This view is supported by a recent report that the loss of asymmetry in the two membrane leaflets leads to domain stabilization [68] …”

Section: Resultssupporting

confidence: 54%

“…This view is supported by a recent report that the loss of asymmetry in the two membrane leaflets leads to domain stabilization. [68] While all of the imaged cultured cells, swollen cells and osmotically-derived vesicles exhibited EphA2-enriched and -depleted domains, about 70 % of the formaldehyde vesicles did not exhibit any EphA2 segregation. For the subset of formaldehyde vesicles that showed EphA2 heterogeneity, we recorded EphA2 intensity ratios for enriched and depleted domains that are smaller than the ratios measured for osmotically-derived vesicles.…”

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

Direct Quantification of Ligand‐Induced Lipid and Protein Microdomains with Distinctive Signaling Properties**

et al. 2022

View full text Add to dashboard Cite

Lipid rafts are ordered lipid domains that are enriched in saturated lipids, such as the ganglioside GM1. While lipid rafts are believed to exist in cells and to serve as signaling platforms through their enrichment in signaling components, they have not been directly observed in the plasma membrane without treatments that artificially cluster GM1 into large lattices. Here, we report that microscopic GM1-enriched domains can form in the plasma membrane of live mammalian cells expressing the EphA2 receptor tyrosine kinase in response to its ligand ephrinA1-Fc. The GM1-enriched microdomains form concomitantly with EphA2-enriched microdomains. To gain insight into how plasma membrane heterogeneity controls signaling, we quantify the degree of EphA2 segregation and study initial EphA2 signaling steps in both EphA2-enriched and EphA2depleted domains. By measuring dissociation constants, we demonstrate that the propensity of EphA2 to oligomerize is similar in EphA2-enriched and -depleted domains. However, surprisingly, EphA2 interacts preferentially with its downstream effector SRC in EphA2-depleted domains. The ability to induce microscopic GM1-enriched domains in live cells using a ligand for a transmembrane receptor will give us unprecedented opportunities to study the biophysical chemistry of lipid rafts.

show abstract

Section: Resultssupporting

confidence: 54%

Section: Discussionmentioning

confidence: 88%

Direct Quantification of Ligand‐Induced Lipid and Protein Microdomains with Distinctive Signaling Properties**

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Thus, changes in lipid compositional asymmetry may regulate the Lo/Ld-like properties in live cell membranes. In addition, in a recent study the London lab found that a loss of lipid asymmetry in GPMVs, which may occur at some point during signal transduction in cells, can induce ordered domain formation 104 Together, these results support the view that phase-like organization in the plasma membranes depends on the lipid composition present. However, this interpretation is an extrapolation from model membranes, either synthetic or GPMVs that lack a cytoskeleton and may have altered asymmetry compared to that of parental cells.…”

Section: Lipids With Exogenous Lipids Is a New Approach For Examining...supporting

confidence: 58%

Section: Exchange Of Endogenous Outer Leaflet Lipids With Exogenous L...mentioning

confidence: 99%

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

Plasma membranes host numerous receptors, sensors, and ion channels involved in cellular signaling. Phase separation within the plasma membrane has emerged as a key biophysical regulator of signaling reactions in multiple physiological and pathological contexts. There is much evidence that plasma membrane composition supports the coexistence of 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 has been 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: cross-linking by multivalent antigen of immunoglobulin E bound to receptor FcεRI and cross-linking 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

“…Lipid domains in which specific lipids and membrane proteins are segregated in the cell membrane are known to be responsible for the several pathways of signal transduction (Simons & Toomre, 2000). Lipid domains have recently also been linked to the structure and composition of lipid bilayers such as lipid asymmetry across the bilayer (Kakuda et al, 2022). Heterogeneity in the lipid bilayer originated in the lateral phase separation or domain formation is also implicated in the action mechanism of the AMPs.…”

Section: Cell-sized Giant Vesiclesmentioning

confidence: 99%

Biomimetic antimicrobial polymers—Design, characterization, antimicrobial, and novel applications

Takahashi

Sovadinová

Vemparala

et al. 2022

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Biomimetic antimicrobial polymers have been an area of great interest as the need for novel antimicrobial compounds grows due to the development of resistance. These polymers were designed and developed to mimic naturally occurring antimicrobial peptides in both physicochemical composition and mechanism of action. These antimicrobial peptide mimetic polymers have been extensively investigated using chemical, biophysical, microbiological, and computational approaches to gain a deeper understanding of the molecular interactions that drive function. These studies have helped inform SARs, mechanism of action, and general physicochemical factors that influence the activity and properties of antimicrobial polymers. However, there are still lingering questions in this field regarding 3D structural patterning, bioavailability, and applicability to alternative targets. In this review, we present a perspective on the development and characterization of several antimicrobial polymers and discuss novel applications of these molecules emerging in the field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

show abstract

Loss of plasma membrane lipid asymmetry can induce ordered domain (raft) formation

Cited by 12 publications

References 45 publications

Direct Quantification of Ligand‐Induced Lipid and Protein Microdomains with Distinctive Signaling Properties**

Direct Quantification of Ligand‐Induced Lipid and Protein Microdomains with Distinctive Signaling Properties**

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

Biomimetic antimicrobial polymers—Design, characterization, antimicrobial, and novel applications

Contact Info

Product

Resources

About