Small Molecule Uptake and Transport in Living and Model Bacterial Membranes

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With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Tessa Calhoun of the University of Tennessee Knoxville is studying how organization in bacterial membranes can alter their interaction with small molecules. Membranes are fundamental biological components, finely tuned via evolution to balance the protection of the living system with an ability to selectively move to the inside of cells molecular cargo essential for life. Membranes are composed of a wide range of different lipid molecules and proteins. These molecules can cluster into domains that result in multiple, unique environments within the same membrane. Using a novel light-probing and microscopy-based approach, Dr. Calhoun plans to make possible the observation of small molecules as they enter membranes and move between these domains within the membrane. Observations with membranes of living bacteria will directly inform on new directions for model membrane formation in artificial cells. Dr. Calhoun is also developing a first-year studies course to bring together women majoring in STEM (Science, Technology, Engineering and Mathematics) fields early in their career development to engage them in dialogue about the importance of diversity, implicit bias, and imposter syndrome.A deeper understanding of how the membrane interacts with exogenous molecules is integral for tailoring molecules designed to target membranes, as well as in developing model systems that facilitate controllable transport. The overall goal of the Calhoun research program is to test hypotheses regarding the functional rules that dictate the behavior of small molecules within the membrane environment of living bacterial cells using second harmonic generation spectroscopy, microscopy, and kinetic modeling. Studies will be conducted on living bacterial cells to provide specific insight on the optimization of small molecule-membrane interactions. This includes measuring dissociation constants for these small molecules and relating these to structural motifs and the presence of functional membrane micro-domain disruptors. The Calhoun group will examine small molecule behavior with model membranes designed to mimic those of bacteria with the intent of improving model membrane design by rational incorporation of membrane ingredients that facilitate transport.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.