Characterization of molecular dynamics and elastic properties of flexible liposomes membranes using Fast-field-cycling NMR

MARZOLA, MARÍA BELÉN; FRAENZA, CARLA C.; ANOARDO, ESTEBAN

Congreso; EUROMAR 2017; 2017

At present, the development of nanometric vesicles fordrug delivery in the human body by different routes has become of greatinterest for the pharmaceutical industry. Flexible liposomes have proved to beuseful for transdermal transport, therefore it is important to measure thebending elastic modulus k of the membrane. This constant has an inverseproportionality relation with the parameter called deformability oradaptability of the vesicles, being one of the most relevant parameters relatedto the penetration dynamics in the skin. In previous works [1-4], a model was presented tointerpret the spin-lattice relaxation rate dispersion of protons, obtained withthe fast field cycling nuclear magnetic relaxometry technique (FFC), forunilamellar liposomes. In addition to providing general information on thelipid dynamics, this model allows us to infer about the elastic properties ofthe liposomes by means of the elastic constant k, which is one of the physical parameters involved inthe model. This model has been validated from measurements of k for cholesterol doped vesicles in order to increasethe value of the constant. On the other hand, in order to extend it in theopposite limit of membrane flexibility, experiments using elastic vesicles wereperformed in this work. Specifically, we analyzed experimental relaxationdispersions obtained at different temperatures (291-328K) for liposomes ofradius of 50nm, composed of SPC (soy phosphatidylcholine) with different ionic(sodium deoxycholate) and nonionic (Tween 80 and BrijO20) detergents added toenhance the membrane flexibility, at concentrations up to 40 mol%.The model was successfully extended for this type ofliposomes. Variations in k were moderate (around 40%) in response to theadditive concentration up to 20mol%. However, we observed some particularchanges in the way diffusion and order fluctuations affect the protonspin-lattice relaxation as detergent concentration is increased, for the threeused detergents. [1] C. J. Meledandri, J.Perlo, E. Farrher, D. F. Brougham, E. Anoardo, Interpretation of MolecularDynamics on Different Time Scales in Unilamellar Vesicles Using Field-CyclingNMR Relaxometry. J. Phys. Chem. B 113: 15532-15540, 2009.[2] J. Perlo, C. J.Meledandri, E. Anoardo, D. F. Brougham Temperature and Size-Dependence ofMembrane Molecular Dynamics in Unilamellar Vesicles by Fast Field-Cycling NMRRelaxometry. J. Phys. Chem. B 115: 3444-3451, 2011.[3] C. C. Fraenza, C. J.Meledandri, E. Anoardo, D. F. Brougham, The Effect of Cholesterol on MembraneDynamics on Different Timescales in Lipid Bilayers from Fast Field‐Cycling NMR Relaxometry Studies of UnilamellarVesicles. ChemPhysChem 15: 425-435, 2014.[4]- G. A. Domingez, J. Perlo, C. C. Fraenza and E.Anoardo, Measurement of the Bending Elastic Modulus in Unilamellar VesiclesMembranes by Fast Field Cycling NMR Relaxometry. Chem. Phys. Lipids 201: 21-27, 2016.