Can a phospholipid moiety that is not associated with any membrane or one that has recently dissociated from a lipoprotein circulate freely in blood plasma? Not necessarily for a very long time but at least for a transient period before the integration into a membrane? Any suggestions or rational explanation of the concept is welcome.
Dear Revathi, Not likely. Even transiently. The cost for hydration of the acylchains would be too much. Hence the reason that DOPC forms bilayers in solution even at very low concentration. So most long chain lipids (diacyl) are unlikely to do this in water. On top of this plasma contains proteins that are likely to bind lipid ensuring there is essentially no free lipid (again diacyl-membrane lipids) free in solution.
I agree with Edgar Kooijman. The equilibrium is so far in the direction of the aggregated state that it is vastly improbable that free DOPC could be determined by any analytical method in whole blood or even in simple saline solution.
The anionic phospholipids, however, may be a different story. The first one I would look at is phosphatidylserine, then phosphatidylglycerol. PS is capable of organizing a vast amount of water in its hydration shell. In this state, it could be possible that a single PS molecule, not interacting with any other phospholipid molecule, could be found in such a hydrated state.
Also, when working with phospholipids, be careful of trace sample contamination by the lyso molecule. The lyso derivatives are powerful detergents.
I would agree with Edgar and suggest that because not only the polar regions bind to proteins but also the apolar acyl chains bind to non-polar regions of proteins, the liftime of transient 'freedom' would be very small.
Dear all, thank for all your suggestions and I think being specific with regard to this question will help a little bit more. I am working on MD simulations for my masters thesis and I needed to get clarified about the fundamental question to put forward the hypothesis.
The protein I am working on transfers lipids from LDL and HDL and the crystal structure bound with the small molecule inhibitor hypothesised that the inhibitor gains access to the middle of the tunnel by displacing a phospho lipid from the pocket. Hence my question. Will the disscociated phospholipid be stable in plasma? or does this event happen when the protein is already bound to either HDL/ LDL implying a case when PL canot not stable in plasma and can immediately diffuse into the HDL/LDL surface thus making the process thermodynamically favourable?
Any inputs/suggesions in these lines is welcome.
Thank you all in advance.
My answer is CAN - at concentrations lower than critical micelle concentration. See http://avantilipids.com/index.php?option=com_content&id=1703&Itemid=422
@Pavol Balgavy: Thank you so much for the link. Since in my case, it is the dissociation of a single molecule of DOPC from the protein, I am assuming it can exist in plasma ( as it is below the critical micelle concentration) and once it exceeds the value of CMC, it could get aggregated and form micelles which may later adhere to or get incorporated into the lipoproteins like HDL/LDL surface or any membrane surface. Is my understanding right?
Kindly provide me your valuable suggestions in this regard.
thank you.
You are right. Remember, that at concentrations>CMC you still have monomers in solution, their concentration = CMC. Approximately, of course.
@Pavol Balgavy : Thank you so much for the explanations.
And thank you all for the suggestions and brainstorming discussions. They were really helpful in getting my basics correct.
Thank you once again.
Dear Revathi,
The question you asked belongs to the era of reductionist science. As such is inappropriate because plasma (or more general blood) cannot be summarized as a unique homogenous substance. If it comes to the physical chemistry answer Pavol provided the right background. However, the CMC dos not matter that much as blood has so many components that would invalidate its importance. Blood proteins especially albumins are main stabilizers or many insoluble elements (as well as the particles you mentioned LDLHDL). So the real question would be what are the relative concentrations as well as multiple equilibrium in particular parts of the circulatory system that your study would be relevant to. That includes the abundance of cells and their lipid content.
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