Referee 1's review:

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.
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This is an interesting manuscript on the influence of loading Penetratin (a cell penetrating peptide) on membrane domains of both liquid disordered fluid and ordered raft-like structures. The present findings reveal that the fluidity of the model membrane has an important role in modulating the perturbation of the domains (the formation of tubulation and vesiculation). The impact of lipid composition on the membrane domains is highlighted.

The manuscript 07-PONE-RA-02688 is suitable for publication in PLoS ONE after having a very minor revision.

My very minor criticisms concern the points that are not clear.

Minor comments on the manuscript:

1) Page 10 (paragraph 2, line 4) & Page 13 (line 2 from bottom): it was written in the text "...was altered deeply as revealed by the hill shaped baseline." This is not very professionally described. The conclusion is correct though: due to vesiculation the Bragg-peaks diminish, but what it is described as the "hill shaped baseline" is the typical form-factor contribution of a bilayer, which simply becomes better visible when the structure factor contribution (diffraction peaks) decrease. I am suggesting to check this part and to improve the terminology at this point. The same accounts also for the sentence "Instead a broad signal appears which distorts the baseline." in page 13 (line 2 from bottom): the conclusion is correct, but the sentence can be improved. It is the form-factor contribution arising from uncorrelated bilayers and not a "distorted baseline". For more information, the authors can check also articles published in literature on the contribution of the form and the structure factors.
2) In page 11, line 3: the interpretation of the additional hump in the WAXS regime to be due to an additional chain packing is reasonable. But if this additional packing arises from curvature or simple some kin of phase separation remains questionable. I am suggesting checking this small hump in the following way: to take the middle pattern and divide it by the upper pattern of panel E. Two points could be examined in this way: first, is it really the only additional little hump or is there another contribution at about 2.4 Å-1? Second, one could judge better the width of the additional scattering contribution. If it is really another fluid lipid contribution arising from strongly curved fluid bilayers, the small hump at 2.1 Å-1 should also be very broad. If it is not broad at all, maybe this contribution is rather arising from phase separated aggregation of peptides.


Detail technical comments:

Summary:
1. Line 1: to add 'that' after 'domains'.
2. Line 2: to add 'the' after 'and'.
3. In Methodology/principal Findings, line 1: to add comma after 'herein'.
4. In Methodology/principal Findings, line 4 and in different parts of the manuscript: to replace 'head groups' by 'headgroups'.

Introduction:
1. Line 9, page 4: to change '(for review see [11-14]' by '(for review see [11-14])'.
2. Paragraph 2 in page 4: to add comma after 'observations' in line 5 & after 'micelles' in line 7.
3. Page 5, line 4: to add comma after 'membranes'.

Results and Discussion:

1. To change the subtitle to 'Discussion'.
2. Page 14, line 6: to add 'nm' after '7.05'.
3. Page 14, Paragraph 2: to add comma after 'conclusion'.
4. Page 15, line 5 from bottom: to add comma after 'case'.
5. Page 15, line 4 from bottom: to remove the word 'perfect'.

Materials and Methods:
Materials

Page 15: to write the chemicals in small letters. To add comma after 'cholesterol' & after (DOPC).
X-ray diffraction:
Page 18: to add '(SAXS)' after small-angle X-ray and 'WAXS' after wide-angle X-ray.

Figure Legends:
Figure 1: to correct the word 'weigth' to 'weight'.
Figure 2: to replace '(non raft)' by 'non-raft'.
Figure 2 & text in page 7: in literature, it is general to prepare dispersions of binary or ternary lipid systems with varying molar ratios. In the manuscript, it was written that the studies were done on dispersions with different weight ratios. This point is not clear in Figure 2. In the text (page 7), it was written '(SM/Chol, 1/1 mol)'. It is good to write these ratios either as weight or molar ratios but not both of them in the same manuscript. It is also good to mention in the caption of Figure 2 (parts A-E) that the experiments done with varying weight ratios.
Figures 5 & S1: it is good to number the figures according to their appearance in the text. No need to have Figure S1 separated from other figures.
Figures 5 & S1: in these figures, it is good to check the decimal separator. It is good to use (.) instead of (,).