Yea, it’s the end of the world… but we can still a cool paper with a gratuitously long TWEET-STORM!!

Check out our new #lipidtime paper in @NatureChemBio:

Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape
https://rdcu.be/b3WCQ 

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tl;dr
- detailed lipidome asymmetry of mammalian PMs
- inner leaflet = much more unsaturated
- simulations: asymmetric physical properties in PM
- confirmed biophys asymmetry in live cells
- protein TMDs conform to lipid asymmetry
- TMD asymmetry conserved for all Eukaryota

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Interested in lipidomics, membrane biophysics, lipid asymmetry, or co-evolution of proteins and lipids? Read on:

We combined lipid-cleaving enzymes with @lipotype lipidomics platform for quantitative, detailed, analysis of lipidomes in individual leaflets of human RBCs.

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Major result: inner PM leaflet has mostly polyunsaturated lipids (more than 2 double bonds in lipid tails) whereas outer leaflet is much more saturated (zero or 1 double bond)

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My friends Ed Lyman and Milka Doktorova plugged detailed compositions into atomistic molecular dynamics simulations.

Predict distinct biophysical properties for inner vs outer leaflets. Outer leaflet more packed, more ordered, less diffusive, smaller hydrophobic defects.

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How to test prediction?! Joseph Lorent (then PD, now group leader @UtrechtUni) came up with genius idea to use reporter dye (Di4) that wont flip between leaflets.

Staining outer leaflet is easy = add outside.

To stain inner leaflet, microinject cells. Amazingly… it works!
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Lifetime of this dye reflects packing of membrane, as described by @lesloew and @Owen_lab_UoB. And Joseph saw that lifetime was much higher in outer leaflet, suggesting that asymmetric lipid packing in PM, with higher packing in outer leaflet.
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Biophysical asymmetry was then confirmed by diffusion measurements in live cells by the brilliant @Sciezgin

Fully consistent with another recent paper: https://www.ncbi.nlm.nih.gov/pubmed/31857388 

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TMDs of PM-resident proteins conform to lipid asymmetry -> thinner inner halves and fatter outer.

TMD asymmetry present across eukaryotic PM proteins

Prediction: the biophysical PM asymmetry Joseph and @sciezgin measure also present throughout Eukaryota

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So proud of this story and so grateful to all @leventallab members and collaborators (and reviewers and editor).

Want to know more? Please reach out on here or by email.