Hydrodynamic Propulsion of Liposomes Electrostatically Attracted to a Lipid Membrane Reveals Size-Dependent Conformational Changes.
The efficiency of lipid nanoparticle uptake across cellular membranes is strongly dependent on the very first interaction step. Detailed understanding of this step is in part hampered by the large heterogeneity in the physicochemical properties of lipid nanoparticles, such as liposomes, making conventional ensemble-averaging methods too blunt to address details of this complex process. Here, we contribute a means to explore whether individual liposomes become deformed upon binding to fluid cell-membrane mimics. This was accomplished by using hydrodynamic forces to control the propulsion of nanoscale liposomes electrostatically attracted to a supported lipid bilayer. In this way, the size of individual liposomes could be determined by simultaneously measuring both their individual drift velocity and diffusivity, revealing that for a radius of ∼45 nm, a close agreement with dynamic light scattering data was observed, while larger liposomes (radius ∼75 nm) displayed a significant deformation unless composed of a gel-phase lipid. The relevance of being able to extract this type of information is discussed in the context of membrane fusion and cellular uptake.
School of Materials Science and Engineering, Nanyang Technological University , 50 Nanyang Avenue, 639798, Singapore.|Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive, 637553, Singapore.
Seyed R
SR
Tabaei
School of Materials Science and Engineering, Nanyang Technological University , 50 Nanyang Avenue, 639798, Singapore.|Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive, 637553, Singapore.
Jurriaan J J
JJ
Gillissen
Department of Applied Physics, Chalmers University of Technology , SE-412 96 Göteborg, Sweden.
Stephan
S
Block
Department of Applied Physics, Chalmers University of Technology , SE-412 96 Göteborg, Sweden.
Fredrik
F
Höök
School of Materials Science and Engineering, Nanyang Technological University , 50 Nanyang Avenue, 639798, Singapore.|Centre for Biomimetic Sensor Science, Nanyang Technological University , 50 Nanyang Drive, 637553, Singapore.|School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, 637459, Singapore.
Nam-Joon
NJ
Cho
D002462:Cell Membrane; D057446:Hydrodynamics; D008051:Lipid Bilayers; D008081:Liposomes; D053758:Nanoparticles
D008051:Lipid Bilayers; D008081:Liposomes
TIRF microscopy; hydrodynamic propulsion; liposome deformation; single particle tracking; supported lipid bilayer