Discovery of new molecules that disrupt cell membranes can find wide applications in antibacterial therapeutics and drug delivery technologies. Such discovery efforts can be accelerated by replacing molecule screening in live cell experiments with molecule screening by cost-effective abiotic sensors that mimic cell membrane environments. For example, recently developed lipid-functionalized single-walled carbon nanotube (SWNT) abiotic sensors were shown to optically detect lipid phase disruptions by screened molecules in real-time. While such abiotic sensors are promising, their many key factors are currently unknown, including the nature of the lipid phase disruption and correlations between the measured optical signal and the disruption type and magnitude. Furthermore, it is unclear if disruptions of the lipid phase on SWNTs are similar in nature and proportional in magnitude to disruptions caused by these molecules in live cell membranes. Here, we characterize the phospholipid-coated SWNT abiotic sensors and their interactions with several cell membrane disruptors using classical atomistic molecular dynamics simulations. The phospholipid coronas in these sensors assume asymmetric arrangements around SWNTs. After addition of disruptors, many of them bind to phospholipid coronas and carpet their surfaces, while the remaining molecules create pores and come in direct contact with SWNT surfaces. For comparison, analogous phospholipid bilayer membranes were simulated in the presence of the same disruptors. The mechanisms of disruption observed in membrane bilayers are then compared to the mechanisms of disruption observed in phospholipid coronas within abiotic sensor models. Our results suggest that lipid-functionalized SWNT abiotic sensors have high potential for accurate screening and effective discovery of new molecules that disrupt cell membranes.

Mechanistic characterization of phospholipid-functionalized single walled carbon nanotube abiotic sensors of molecules that disrupt cell membranes

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