All of the references to this I can find refer to enzymes like Flippase making it 'easier' or 'more likely' that the translocation will occur, rather than actually make it possible.

The following is from Alberts

In the ER, however, phospholipids equilibrate across the membrane within minutes, which is almost 100,000 times faster than can be accounted for by spontaneous “flip-flop.”

Does this mean that left unattended, any phospholipid membrane will 'flip-flop' spontaneously, just very slowly, and can this be observed?


Bilayer components will 'flip-flop' at measurable rates, but these are very different for different lipid classes. Here are the results of an experiment using fluorescently-labelled analogues.

Bai, JN and Pagano, RE (1997) Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles. Biochemistry 36:8840-8848 DOI: 10.1021/bi970145r

The authors followed the transbilayer (flip-flop) and interbilayer movement of fluorescently-labelled analogues of various membrane lipids: sphingomyelin (C-5-DMB-SM), ceramide (C-5-DMB-Cer), phosphatidylcholine (C-5-DMB-PC) and diacylglycerol (C-5-DMB-DAG) in a system of unilamellar vesicles consisting of 1-palmitoyl-2-oleoyl phosphatidylcholine.

The results were analysed in terms of a model in which the labelled molecules could move between vesicles and between the two monolayers of the bilayer.

half times:
            interbilayer    transbilayer (flip-flop)
C-5-DMB-SM  >21 s           3.3 h               
C-5-DMB-Cer 350 s           22 min
C-5-DMB-PC  400 s           7.5 h
C-5-DMB-DAG 100 h           70 ms

So, for the phospholipid tested the half-time for flip-flop was 7.5 hours.

  • $\begingroup$ This answer is a good starting point and gives a flavor of the issue. I think it's worth noting though that there is a pretty big variation between different experiments on flip-flop rates. I think there are orders of magnitude changes, and so a more recent reference would be good. (Anyone interested in this could probably look at the 1997 ref. and see what papers cite it in Google Scholar.) $\endgroup$
    – AJK
    Nov 16 '16 at 2:26

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