Lipid Polymorphisms and Membrane Shape

Frolov, Vadim A.; Shnyrova, Anna V.; Zimmerberg, Joshua

doi:10.1101/cshperspect.a004747

Cited by 174 publications

(127 citation statements)

References 79 publications

(117 reference statements)

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“…The final organization of lipids depends on their nature, concentration, temperature, and geometric form. 8 If ions or molecules are present during the formulation process, they can be encapsulated inside these membranes.…”

Section: The Physicochemistry Of Liposomesmentioning

confidence: 99%

Liposomes as nanomedical devices

Bozzuto¹,

Molinari²

2015

IJN

1,794

1,114

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Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials.

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Section: The Physicochemistry Of Liposomesmentioning

confidence: 99%

Liposomes as nanomedical devices

Bozzuto¹,

Molinari²

2015

IJN

1,794

1,114

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“…This ability of lipids to assemble into different structural associations is referred to as lipid polymorphisms ( Fig. 1) (Frolov et al 2011).…”

Section: Lipidsmentioning

confidence: 99%

Membrane Organization and Lipid Rafts

Simons¹,

Sampaio²

2011

Cold Spring Harbor Perspectives in Biology

917

806

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Cell membranes are composed of a lipid bilayer, containing proteins that span the bilayer and/or interact with the lipids on either side of the two leaflets. Although recent advances in lipid analytics show that membranes in eukaryotic cells contain hundreds of different lipid species, the function of this lipid diversity remains enigmatic. The basic structure of cell membranes is the lipid bilayer, composed of two apposing leaflets, forming a twodimensional liquid with fascinating properties designed to perform the functions cells require. To coordinate these functions, the bilayer has evolved the propensity to segregate its constituents laterally. This capability is based on dynamic liquid-liquid immiscibility and underlies the raft concept of membrane subcompartmentalization. This principle combines the potential for sphingolipid-cholesterol self-assembly with protein specificity to focus and regulate membrane bioactivity. Here we will review the emerging principles of membrane architecture with special emphasis on lipid organization and domain formation.

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“…Differences in tension between the two leaflets not only result in an asymmetry of the lateral pressure profile, but also generate additional forces across the membrane known as membrane torque (36,38). Typically, such asymmetric changes are elicited either by alterations in membrane curvature or via insertion of noncylindrical lipids into individual leaflets (36,39).…”

Section: Significancementioning

confidence: 99%

Asymmetric mechanosensitivity in a eukaryotic ion channel

Clausen

Jarerattanachat

Carpenter

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Living organisms perceive and respond to a diverse range of mechanical stimuli. A variety of mechanosensitive ion channels have evolved to facilitate these responses, but the molecular mechanisms underlying their exquisite sensitivity to different forces within the membrane remains unclear. TREK-2 is a mammalian twopore domain (K2P) K + channel important for mechanosensation, and recent studies have shown how increased membrane tension favors a more expanded conformation of the channel within the membrane. These channels respond to a complex range of mechanical stimuli, however, and it is uncertain how differences in tension between the inner and outer leaflets of the membrane contribute to this process. To examine this, we have combined computational approaches with functional studies of oppositely oriented single channels within the same lipid bilayer. Our results reveal how the asymmetric structure of TREK-2 allows it to distinguish a broad profile of forces within the membrane, and illustrate the mechanisms that eukaryotic mechanosensitive ion channels may use to detect and fine-tune their responses to different mechanical stimuli.any forms of sensory perception in higher organisms depend on the rapid conversion of mechanical and physical stimuli into the electrochemical language of nerve and muscle cells (1). These transduction mechanisms often involve "mechanosensitive" (MS) ion channels that are able to rapidly convert physicomechanical stimuli into the electrical signals required for complex physiological responses (e.g., touch, pain, hearing, proprioception), as well those mechanical signals that play key roles in development and cell-cell communication (2). The enormous complexity and diversity of these sensory responses suggests that a variety of molecular mechanisms are likely responsible; for example, while some channels are regulated via physical coupling to proteins of the cytoskeleton and/or cell matrix, others respond directly to changes in lipid membrane tension (3). The precise structural and physical mechanisms underlying these processes remain poorly understood, however (4-6).Our current understanding of how membrane tension directly regulates ion channel gating is largely derived from studies of prokaryotic MS ion channels involved in the control of bacterial turgor pressure (7,8). The open state of these MS channels has a larger cross-sectional area than the closed state within the membrane, and stretch-induced changes in the forces within the bilayer stabilize the expanded open-state conformation. This is commonly referred to as the force-from-lipid principle of mechanosensitivity (9). Similar physical principles are thought to regulate many eukaryotic MS channels (5, 10).Typically, the functional activity of MS ion channels is examined in pipette-based patch-clamp recordings in which negative or positive pressures are used to alter bilayer tension. These pressure changes stretch the membrane to alter the lateral pressure profile, the complex profile of forces that vary with location acro...

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Lipid Polymorphisms and Membrane Shape

Cited by 174 publications

References 79 publications

Liposomes as nanomedical devices

Liposomes as nanomedical devices

Membrane Organization and Lipid Rafts

Asymmetric mechanosensitivity in a eukaryotic ion channel

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