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Looks like somebody's salty: neutrons reveal how ions influence model cell membranes

A team of researchers at the ILL investigated how salt alters the shape of lipid vesicles.

All life forms, from bacteria to animals, contain cells and organelles, which are surrounded by membranes. The main constituents of these membranes are lipids—molecules made of hydrophilic (water loving) "heads" and hydrophobic (water fearing) "tails". In the presence of water, these molecules form closed, hollow spherical structures called vesicles. These vesicles can also be used as carriers for drugs and vaccines.

In biological systems, natural or artificial, substances such as salts are usually present. Normally, these do not cross lipid membranes. If the concentration of such components (also known as “osmolytes”) inside and outside the vesicle differs, a so-called osmotic pressure builds up and water will permeate the membrane to even out osmolyte concentrations – if the concentration inside the closed structure is higher, water will come inside the vesicle, thereby making it swell; if, however, the concentration outside the vesicle is higher, water will leave the vesicle, deflating it.

Vesicles are often produced in pure water and therefore the influence of osmolytes is rarely investigated. However, the biological relevance of osmolytes implies that their influence is important to understand. This topic was studied by Alice Piccinini's as part of her PhD thesis, jointly co-supervised by Anja Winter at the University of Keele, UK, and Sylvain Prévost at the ILL. "We wanted to understand how adding different osmolytes, in particular salts, but also electrically neutral molecules such as glucose and a simple oligomer, alter vesicles consisting of model lipids," says Piccinini, who is the first author of a recently published article based on this work.

The team used small-angle neutron scattering (SANS) in ILL instrument D22 for their study, which allowed them to probe the vesicle structure while keeping their samples intact – a particular strength of scattering techniques. In addition, dissolving the vesicles in heavy water (D2O) instead of normal, light water (H2O) enabled them to visualise the lipid layers in greater detail. This allowed them to draw conclusions about the shapes of the vesicles when subjected to osmotic pressure.

"A classical buffer used in biology and for pharmaceutical products is PBS (phosphate-buffered saline). PBS matches the salinity and osmolarity of the human body," says Sylvain Prévost, SANS scientist at the ILL. Interestingly, the team discovered that the vesicle’s shape and structure depended how they were made (either in D2O or PBS) and how much or which type of osmolyte was added. In the presence of PBS, vesicles with several membranes inside each other were produced, which is undesirable for most scientific studies or pharmaceutical applications. Temperature and osmotic stress affected the shape of the vesicles, which may form very flat structures that could even go on to form invaginations.

Overall, this work allowed obtaining highly detailed insights into the often well-hidden world of lipid vesicles. "In addition to inspiring further, mechanistic studies on lipid vesicles, our results are relevant for practical processes underlying vesicle formation, such as the design of therapeutic formulations," summarises Alice Piccinini. “Obtaining easily very elongated and flat vesicles, or double-walled liposomes, can be an asset for drug release, for example.”


Reference: Piccinini, A., Whitten, A. E., Winter, A., & Prévost, S. (2025). The effect of phosphate buffered saline and osmotic stress on phosphatidylcholine vesicles. Journal of Colloid and Interface Science, 691, 137363. 

doi.org/10.1016/j.jcis.2025.137363

ILL instrument: D22

ILL contact: Sylvain Prévost