Comparative Deformability Characterization On HIV Variants Using a Solid State Nanopore
Nanoscale lipid vesicles, such as enveloped viruses, lysosomes and exosomes, play a significant role in material transport in biological systems. Membrane deformation of these naturally occurring nanocarriers is a defining factor in maintaining their functionality. De- spite the great significance to biologists and biophysicists, experimental investigations into membrane deformablity are currently lacking due to technical challenges of studying mem- brane deformation especially at the sub-micron scale. Optical microscopy lacks sufficient resolution to capture deformation at the nanoscale. Other techniques, such as atomic force microscopy, require laborious procedures and are intrinsically low-throughput. In this paper, we report a new technique based on nanopore resistive pulse sensing for characterizing the deformablity of lipid vesicles at the nanoscale. We used pseudo-type Human Immunodeficiency Viruses type 1 (HIV-1) as a model system to demonstrate the proof-of-concept experiments. The deformability of immature and mature viruses were compared based on their respective resistive pulse signals. In addition, the effects of cholesterol and protein on the deformability of mature viruses were investigated by genetically/chemically modifying the membranes. Furthermore, a recapture protocol was employed to demonstrate the ability of nanopore resistive pulse sensing in characterizing the deformation of a single virus as opposed to average ensemble measurements.