Collaborative Research: Quantitative Analysis of Liposome Deformation at Nanoscale Using Resistive Pulse Sensing in Solid State Nanopores

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Tiny lipid sacs, called liposomes, play a crucial role in living cells as means to store and transport material in and out of the cell. The key task of liposomes (storage and delivery to targets) requires them to be flexible enough to merge with target membranes in order to deliver their cargos, and yet to have sufficient structural stability to maintain integrity without rupturing and losing the stored material in the naturally dynamic biological environments. Therefore, understanding the mechanics of liposomes is of great interest to both fundamental and applied scientists who are developing artificial, biomimetic liposomes as targeted drug/gene delivery systems for better therapeutics. A major challenge however, is the lack of efficient engineering tools to probe the mechanical flexibility of the sub-cellular, nanoscale liposomes. The research addresses this need by developing a novel method based on nanopore technology that uses electric fields to deform liposomes and electrical measurements to characterize their shape. The overall goal is to characterize the mechanical flexibility of nano-liposomes with the ultimate goal to establish a method to study mechanical properties of nanoscale objects such as viruses and other biological samples at cellular/molecular level.This project will advance the engineering tools for mechanical characterization of soft biological materials at the micro/nanoscale. The technology uses nanopore resistive pulse sensing to detect membrane deformation. As liposomes translocate through a nanopore, they experience strong electric stresses and physical confinement, which cause deformation. In this project, liposome shapes will be inferred from ionic current blockade, i.e., the sharp change (pulse) in ohmic resistance when a liposome is present in the pore. A theoretical model for liposome deformation in the nanopore will be developed to yield membrane mechanical properties. The method will enable both high-throughput and single-particle resolution because (1) thousands of liposomes pass through the nanopore and a resistive pulse will be recorded for each individual one, and (2) thousands of measurements on a single liposome can be made by alternating the applied electric field direction to drive back-and-forth translocation. In broader terms, this method will enable studying mechanobiology at novel unprecedented scales, which is single-virus and single-particle level.