posted on 2024-03-13, 18:21authored byNegin Gooran, Sue Woon Tan, Shelli L. Frey, Joshua A. Jackman
Triton X-100 (TX-100) is a membrane-disrupting detergent
that is
widely used to inactivate membrane-enveloped viral pathogens, yet
is being phased out due to environmental safety concerns. Intense
efforts are underway to discover regulatory acceptable detergents
to replace TX-100, but there is scarce mechanistic understanding about
how these other detergents disrupt phospholipid membranes and hence
which ones are suitable to replace TX-100 from a biophysical interaction
perspective. Herein, using the quartz crystal microbalance-dissipation
(QCM-D) and electrochemical impedance spectroscopy (EIS) techniques
in combination with supported lipid membrane platforms, we characterized
the membrane-disruptive properties of a panel of TX-100 replacement
candidates with varying antiviral activities and identified two distinct
classes of membrane-interacting detergents with different critical
micelle concentration (CMC) dependencies and biophysical mechanisms.
While all tested detergents formed micelles, only a subset of the
detergents caused CMC-dependent membrane solubilization similarly
to that of TX-100, whereas other detergents adsorbed irreversibly
to lipid membrane interfaces in a CMC-independent manner. We compared
these biophysical results to virus inactivation data, which led us
to identify that certain membrane-interaction profiles contribute
to greater antiviral activity and such insights can help with the
discovery and validation of antiviral detergents to replace TX-100.