Membrane solubilization
by sodium dodecyl sulfate (SDS) is indispensable
for many established biotechnological applications, including viral
inactivation and protein extraction. Although the ensemble thermodynamics
have been thoroughly explored, the underlying molecular dynamics have
remained inaccessible, owing to major limitations of traditional measurement
tools. Here, we integrate multiple advanced biophysical approaches
to gain multiangle insight into the time-dependence and fundamental
kinetic steps associated with the solubilization of single submicron
sized vesicles in response to SDS. We find that the accumulation of
SDS molecules on intact vesicles triggers biphasic solubilization
kinetics comprising an initial vesicle expansion event followed by
rapid lipid loss and micellization. Our findings support a general
mechanism of detergent-induced membrane solubilization, and we expect
that the framework of correlative biophysical technologies presented
here will form a general platform for elucidating the complex kinetics
of membrane perturbation induced by a wide variety of surfactants
and disrupting agents.