The topic of ion interactions with membranes is complicated since in the model it depends on both ion and lipid parameters. There are probably inaccuracies in both of these.
I think that the ion issue discussed in the manuscript could be divided into two different problems:
1) the partitioning of sodium ions is probably too high and
2) the membrane response to the ion partition is wrong.
It could be that the first issue is solely related to the ion force field and the second issue to the lipid force field, however also cross-relation is possible. For example, it could be that the Sodium partitioning is too high because membrane response has too low energy cost. Several other scenarios are also possible.
There is at least one thing which could be assessed to clarify the issue: The electronic polarizability. Recently, it has been suggested that this could be partially taken into account by scaling the charges [Leontyev et al. PCCP 13, 2613 (2011)]. It would be interesting to try out if this approach would improve the partitioning issue (1). I do not believe, however, that the membrane response issue (2) could be fixed simply by this approach; there is, namely, a problem in the membrane energies in all the other cases as well.
Samuli Ollila
Aalto University
I found a relevant publication related to the ion-membrane interactions which I have not cited in the manuscript: Filippov et al. Chem. Phys. Lipids 159, 81 (2009) http://dx.doi.org/10.1016/j.chemphyslip.2009.03.007
ReplyDeleteThey measure the lipid lateral diffusion coefficients with different ion concentrations by using NMR. The lateral diffusion of DOPC is not affected up to 0.27 M concentration of NaCl, and 0.1 M concentration of CaCl_2. I find this important since one of the evidence presented for the Na+ binding into a PC headgroup has been the decreased lateral diffusion coefficient of membrane probes (Böckmann et al. Biophys. J. 85, 1647 (2003) http://dx.doi.org/10.1016/S0006-3495(03)74594-9)
Since Filippov et al. do not find the decrease with NMR measurements they write:
"Thus, it seems that we are forced to conclude
that the lateral diffusion coefficients obtained by the fluorescence
methods used by Böckmann et al. (2003) are strongly dependent
on the fluorescent probe molecule and should be taken with
caution."
While reading the literature more carefully I realised that the order parameters for g1 and g2 as a function of ion concentration are not actually measured in Akutsu et al. Biochemisry 20, 7366 (1981), Ref. 36 in the manuscript. However, they show that ions do not affect to the g3 order parameter and to the order parameters of the first carbons in the acyl chains. Then they conclude that:
ReplyDelete"The addition of metal ions has practically no effect on the quadrupole splittings of the glycerol backbone or the fatty acyl chain segments, suggesting that the interaction with the lipid bilayer is limited to the polar region."
In principle it is, however, possible that ions affect the g2 and/or g1 order parameter since that effect is not explicitly measured. I find it unlikely, though. I am not aware of any other experimental data where that would be measured either. I think that nowdays this could be done with ¹³C NMR without specifically dueterated samples.
In conclusion, I think that the experimental data for g1 and g2 should be removed from Fig. 4 before actual data is found from literature, or measured by somebody.