Biological membranes normally have different composition of lipids on the inside and outside (ref 1, ref 2). This is maintained both by how new lipids are added to membranes, and by specialized enzymes (flippases). Certain lipids being on the "wrong side" is an important signal (eg for apoptosis).

My question is: how fast do lipids from the inside and outside exchange spontaneously? In a patch of membrane with no enzymes, how long until half the "inside" lipids have flipped to the outside and vice versa through simple diffusion?

I did a search but couldn't find any specific paper that measures the spontaneous exchange rate. I'd be very interested in a definitive answer - could be just order of magnitude, but based on real measurements.

UPDATE This is important for figuring out the inside/outside composition of membranes in real scenarios when they're no longer being maintained in an asymmetric state: for example enveloped viruses, but also microparticles, dead cells, etc.


1 Answer 1


A cursory search seems to show at least a few papers using sum-frequency vibrational spectroscopy to measure rates of flip-flopping/transverse diffusion in lipid bilayers.

This paper in particular ("1,2-Diacyl-Phosphatidylcholine Flip-Flop Measured Directly by Sum-Frequency Vibrational Spectroscopy") cites an activation barrier of 79 kJ/mol which corresponds to a rate on the order of 10^-4/s.

There is also this review which seems to have more information on the topic: http://dx.doi.org/10.1021/acs.accounts.6b00435.

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    $\begingroup$ Very well. Also, this paper may be helpful, as it has some data about the activity of Mdr2, a phosphatidylcholine flippase by the measurement of time and relative fluorescence . One may also find the rate of movement implicitly . sciencedirect.com/science/article/abs/pii/0092867494904464 @Spencer Guo by the way, the first link of yours is not working. $\endgroup$ Jan 1, 2021 at 7:06
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    $\begingroup$ @SpencerGuo - Good stuff, thanks. From the first paper, looks like at human body temperature the half lifes are < 1 min for DMPC, 9 min for DPPC, > 300 min for DSPC. Very dependent on lipid tail length... The review is also excellent. $\endgroup$
    – Alex I
    Jan 1, 2021 at 7:50
  • $\begingroup$ @AlexI Yes I should have noted that the barriers are quite strongly lipid identity-dependent. $\endgroup$ Jan 7, 2021 at 22:20

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