Infection-on-a-chip for viral entry modeling

Abstract Reassembling cell membranes on functional supports can facilitate sensing and studying biorecognition events at the cell surface. Here, we introduce a bioelectrical sensing platform on which biomimetic supported lipid bilayers (SLBs) are assembled and electrical signals are used to detect distinct SARS-CoV-2 virus entry pathways. By recreating the host microenvironmental signals, we were able to initiate and monitor fusion events between SLBs and Spike-decorated virus pseudoparticles (VPPs) via changes in membrane resistance using electrochemical impedance spectroscopy (EIS) and confirm independently by total internal reflection microscope (TIRF). EIS data indicated that fluctuations in resistance vary depending on the VPP/SLB interactions (i.e. binding versus fusion) and our sensing platform can distinguish between the two events. We show that this sensing platform offers complete control over components presented, allows for the SLB to model either the host cell or viral surfaces, and can distinguish between virus variants with different fusogenicities. Though SARS-CoV-2 VPPs and biomimetic SLBs serve as a model system, we anticipate that the full capacity of this platform can be realized by expanding to other enveloped viruses and different cell lines to quantifiably explore virus/host interactions, which can be tuned to mimic the membrane environment of a particular host.