Biological cells possess a membrane, which keeps the constituents in the cell, prevents the penetration of unwanted substances, and triggers the transport of nutrients and waste products. Such membranes can confine drugs for the transport to their target and could also be prepared from artificial phospholipids. They are stable in planar and spherical arrangements. Recently, metastable facetted liposomes have been discovered. These liposomes exhibit the specific property that they can release their cargo upon external and internal physical stimuli. Our team has demonstrated that changes in the medically relevant temperature range give rise to structural changes of selected liposomes [Langmuir 35 (2019) 11210]. A more important study [Materials Today BIO 1 (2019) 100003] provides a robust and cutting-edge combination of synchrotron radiation-based small-angle X-ray scattering and microfluidics to investigate the in situ structural modifications and shape deformations of non-spherical liposomes about 100 nm in diameter when flowing in constricted blood vessels, here mimicked by microfluidics channels. This sophisticated approach resulted in real-time data that revealed insights into the intriguing flow-induced behavior of nanometer-sized liposomes. The mean size and shape of the non-spherical, facetted, and relatively stiff liposomes as well as their average bilayer thickness, which could be spatially detected under flow conditions akin to the ones occurring in constricted blood vessels are altered at the entry and the exit of the constrictions in the channels of the microfluidic device. The bilayer thickness increase of the faceted liposomes is explained and convincingly illustrated by the hydrodynamical pressure-gradient, which induced the loss of interdigitation between the phospholipid acyl chains. Therefore, the hydrodynamically induced pressure-gradient force rather than the anticipated wall-shear stress could trigger the structural modifications of nanometer-sized liposomes and the related cargo release at vessel constrictions. Furthermore, analyzing selected flow rates below the maximal values during pulsatile flows in healthy and atherosclerotic blood vessels, the impact of the hydrodynamic stimuli on shape and structure of the non-spherical liposomes was identified.
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