Our research program aims to directly probe how the complexity of living bacterial membranes impacts the
adsorption, transport, and domain association of small molecules, including antibiotics. To address these
points, we will leverage nonlinear spectroscopy and microscopy techniques, speci¿cally second harmonic
generation, to map the dynamic behavior. A key to our methodology is the ability to conduct the proposed
experiments on living cells instead of model systems. For the next 5 years, our program goals are to
(1) extract the key factors that in¿uence the adsorption and membrane organization of small molecule
membrane probes, (2) quantitatively assess the adsorption of tetracycline antibiotics and manipulate their
movement within and through the membranes of different species of bacteria, and (3) examine the spatial
dependence of small molecule-membrane interactions on individual bacteria as well as within bio¿lms.
Together these studies will elucidate the role of how parameters including curvature, membrane domains,
and the cell wall mediate small molecule uptake. We envision that this insight will provide new directions
in the continued pursuit of improved antibiotics.