Physical mechanisms of micro- and nanodomain formation in multicomponent lipid membranes

Schmid, Friederike

doi:10.1016/j.bbamem.2016.10.021

Cited by 104 publications

(112 citation statements)

References 214 publications

(412 reference statements)

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“…Therefore, a feasible strategy is to begin with the simplest model membranes that grasp only the most essential aspects of their biological counterparts, and then to move forward step-by-step in complexity. In this work, we employ the simplest model in which nanodomains might form 8, 9 : the well characterized mixture 10, 11 of cholesterol and dipalmitoylphosphatidylcholine (DPPC). The canonical phase diagram for the DPPC–cholesterol system (see Fig.…”

Section: Introductionmentioning

confidence: 99%

Nanoscale Membrane Domain Formation Driven by Cholesterol

Javanainen

Martinez‐Seara

Vattulainen

2017

Sci Rep

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Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic experimental techniques due to their small size, yet there is also a lack of atomistic simulation models able to describe spontaneous nanodomain formation in sufficiently simple but biologically relevant complex membranes. Here we use atomistic simulations to consider a binary mixture of saturated dipalmitoylphosphatidylcholine and cholesterol — the “minimal standard” for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets. The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip–flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains. The model considered explains a plethora of controversial experimental results and provides an excellent basis for further computational studies on nanodomains. Furthermore, the results highlight the role of cholesterol as a key player in the modulation of nanodomains for membrane protein function.

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Section: Introductionmentioning

confidence: 99%

Nanoscale Membrane Domain Formation Driven by Cholesterol

Javanainen

Martinez‐Seara

Vattulainen

2017

Sci Rep

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“…Even in bilayers containing only simple lipid mixtures, in the absence of proteins, lipid sorting is observed [12,13,14,15]. A thorough and recent review describes the two mechanisms that can drive lipid sorting in lipid-only systems [16]. These include lipid–lipid phase separation, where lipids organize based on similar tail saturation and the sorted domains are stabilized by cholesterol.…”

Section: Introductionmentioning

confidence: 99%

“…The second mechanism by which lipid microdomains form requires lipid mixtures that are not globally phase-separated, but rather have micro-emulsions or regions where lipids locally separate. These micro-emulsions can be stabilized in a variety of ways, including the addition of surfactants that ease the line tension at the interface between lipid domains or by local regions of membrane curvature [16]. In both mechanisms, membrane shape plays a role in sorting lipids or stabilizing lipid domains.…”

Section: Introductionmentioning

confidence: 99%

Single Lipid Molecule Dynamics on Supported Lipid Bilayers with Membrane Curvature

et al. 2017

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The plasma membrane is a highly compartmentalized, dynamic material and this organization is essential for a wide variety of cellular processes. Nanoscale domains allow proteins to organize for cell signaling, endo- and exocytosis, and other essential processes. Even in the absence of proteins, lipids have the ability to organize into domains as a result of a variety of chemical and physical interactions. One feature of membranes that affects lipid domain formation is membrane curvature. To directly test the role of curvature in lipid sorting, we measured the accumulation of two similar lipids, 1,2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DHPE) and hexadecanoic acid (HDA), using a supported lipid bilayer that was assembled over a nanopatterned surface to obtain regions of membrane curvature. Both lipids studied contain 16 carbon, saturated tails and a head group tag for fluorescence microscopy measurements. The accumulation of lipids at curvatures ranging from 28 nm to 55 nm radii was measured and fluorescein labeled DHPE accumulated more than fluorescein labeled HDA at regions of membrane curvature. We then tested whether single biotinylated DHPE molecules sense curvature using single particle tracking methods. Similar to groups of fluorescein labeled DHPE accumulating at curvature, the dynamics of single molecules of biotinylated DHPE was also affected by membrane curvature and highly confined motion was observed.

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“…The exact PL composition varies with cell type and does not simply reflect the PL composition of the PM or the raft and non-raft domains contained therein. Due to differences in PL molecular shape and charge, lateral domains containing different molecular species can form in a membrane due to variations in local curvature (150,151). Thus, the PM PL molecules will be sorted to form the highly curved exovesiculated domain created by ABCA1 activity (Fig.…”

Section: Characterization Of Nascent Hdlmentioning

confidence: 99%