pH-Modulated Nanoarchitectonics for Enhancement of Multivalency-Induced Vesicle Shape Deformation at Receptor-Presenting Lipid Membrane Interfaces

Journal article, 2023

Multivalent ligand-receptor interactions betweenreceptor-presentinglipid membranes and ligand-modified biological and biomimetic nanoparticlesinfluence cellular entry and fusion processes. Environmental pH changescan drive these membrane-related interactions by affecting membranenanomechanical properties. Quantitatively, however, the correspondingeffects on high-curvature, sub-100 nm lipid vesicles are scarcelyunderstood, especially in the multivalent binding context. Herein,we employed the label-free localized surface plasmon resonance (LSPR)sensing technique to track the multivalent attachment kinetics, shapedeformation, and surface coverage of biotin ligand-functionalized,zwitterionic lipid vesicles with different ligand densities on a streptavidinreceptor-coated supported lipid bilayer under varying pH conditions(4.5, 6, 7.5). Our results demonstrate that more extensive multivalentinteractions caused greater vesicle shape deformation across the testedpH conditions, which affected vesicle surface packing as well. Notably,there were also pH-specific differences, i.e., a higher degree ofvesicle shape deformation was triggered at a lower multivalent bindingenergy in pH 4.5 than in pH 6 and 7.5 conditions. These findings supportthat the nanomechanical properties of high-curvature lipid membranes,especially the membrane bending energy and the corresponding responsivenessto multivalent binding interactions, are sensitive to solution pH,and indicate that multivalency-induced vesicle shape deformation occursslightly more readily in acidic pH conditions relevant to biologicalenvironments.