Thanks Zeljka for this reading advice: Predicting the Time of Entry of Nanoparticles in Lipid Membranes, by Changyang Liu et al.https://platform.twitter.com/widgets.js
So I did. Not the details of the simulations (beyond my expertise) but the introduction and some key aspects of the work, including the choice of nanomaterials and the comparison with experimental results.
I have annotated the article using hypothes.is. You can read those annotations here. There are several things in the introduction which are pretty common in the bionano litterature but nevertheless irritating.
So, for example, if you read the title and you are not an expert in this field, you will be thinking that nanoparticles in general enter lipid membranes. But do they? The authors (nearly) clarify in the introduction that in fact they don’t, e.g. “… proteins or nanoparticles (NPs) […] hydrophilicity and large size hamper direct diffusion through the membrane lipid bilayer” and ” In general, cells do not permit access of polar macromolecules to their cytosol, and phospholipid membranes constitute an effective barrier“. But then, they also state the contrary, i.e. that nanoparticle do penetrate cell membranes (science fiction?), e.g. “Smaller nanoparticles can instead cross the membrane by passive transport, that is, by displacing, sometimes irreversibly, the lipids or by diffusing in the hydrophobic region of the membrane and then on the other side“. That extraordinary statement is not supported by references. Which one is true? How do we reconcile these contradictory statements?
The introduction then moves away from the experimental world towards the world of simulation. That is fine (and largely beyond my expertise), but it means the rationale for studying nanoparticles penetration in membranes rests on the juxtaposition of two contradictory statements, one of which is not backed by experimental results.
So the introduction (and title) is about nanoparticles (in general) going through membranes, but the nanoparticles modeled (see below, reproduced from their Figure 8) are three tiny (even for nanoparticles) objects. Their sizes are certainly not typical of contrast agents or drug delivery vehicles discussed in the introduction.
And those nanoparticles have another feature really not typical of nanoparticles for biomedical applications: they are extremely hydrophobic. Their partition coefficient between lipids and water is 100% (table 1 in the paper). This is very far from your typical nanoparticle. And it raises another question related to the experiments presented in the last figure of the article.
UPDATE 24/09 (following Alan’s comment):
Fig 9 (reproduced below) shows the “leaking” of GQDs from giant vesicles (~50-70 micrometers). These are spinning disk confocal images taken with a 60X objectives. So we should see a section through the vesicle (I think it is more likely to be a total intensity projection but they don’t say).
If those “particles” love the membranes so much, they should simply accumulate in membranes, not diffuse through. Why don’t we see any accumulation in the membranes in Figure 9?
I can’t work out exactly the details of the comparison between the experimental data and the simulations so I will get in touch with the authors.