Natural cell membranes are composed of a thin lipid bilayer (LB) that forms a continuous barrier around the cell, and abundant membrane proteins that play key functions of the cell and stabilize LB. The cell membrane sits on a supporting intracellular matrix called cytoskeleton layer that defines cell shape and further stabilizes LB. Ion channels and molecular receptors of membrane proteins on LB are the main targets of fundamental research and pharmaceutical drugs. As such, model LBs have been the crucial platform to study transport and signaling processes of membrane proteins. However, current model LBs suffer from notorious limitations including (1) short LB lifetime, (2) fluidic and/or electrical inaccessibility to both sides of the membranes, and (3) lack of the rich constituents of natural cell membrane. Addressing these limitations of model LB systems should significantly expedite both fundamental biological studies and pharmaceutical drug screenings.
This proposal outlines a five-year program of integrated research and educational activities focusing on the development of highly stable lipid bilayers (HSLB) in microfluidic networks. The investigator proposes to fabricate LB on a freestanding, semi-permeable and mechanically robust biopolymer membrane, the first time such a configuration being pursued. The work will assess the hypothesis that the supporting membrane can serve as a model cytoskeleton layer for the lipid bilayer with high stability that presents in natural cell membranes. The fabricated HSLB will be characterized and compared with current model LBs, applied to study ion channel activities and the virus-cell membrane fusion process, and scaled up for other research and industrial users. Compared to current suspended and supported LBs, the developed HSLB system will provide long-term stability, better replication of cell membranes and ease of scaling-up, as well as enabling simultaneous fluidic, electrical and optical measurements and manipulations. When fully established, the HSLB platform can be a game-changer for studying fundamental membrane biology and identifying membrane-associated novel drug targets, which are greatly limited by the current model LB systems. Besides bioengineers developing microfluidic and Lab-on-a-Chip devices, this research will be of interest to scientists studying biopolymer materials and membrane protein activities, industrial researchers investigating drug targets and high throughput screening, and educators teaching biomaterials and biomicrosystems.
