Virginia Via Research Day Book 2026

Medical Student Research Biomedical

12 BILAYER FUSION/FISSION PORE STRUCTURE IS DETERMINED BY THICKNESS AND SPONTANEOUS CURVATURE PREFERENCES: SIMULATIONS OF LIPIDS WITH STEROLS AND GENERAL ANESTHETICS

Jay Dadhania, OMS-I; Noah Englander; Amirali Hossein, PhD; Alexander Sodt, PhD Corresponding author:jaydadhania0702@gmail.com

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

The mechanism of action of general anesthetics remains mysterious and is likely a combination of many different factors. The potency of many general anesthetics is highly correlated with their hydrophobicity, suggesting a membrane-dependent, non-specific effect. Membrane-reshaping is a key process in cellular homeostasis that allows vesicle traffic to and from the plasma membrane. Our lab has developed methodology for predicting the effect of small molecules and lipids on energetic barriers to reshaping membranes, with a molecule's ability to thin or thicken a membrane strongly suggestive of its effect on reshaping. Here, we

apply that methodology to a set of propofol analogs to correlate their anesthetic potency with their mechanical effect on reshaping. First, we find that a key property of propofol (local chemical shielding of its hydrophobic group) correlates strongly with its position in the bilayer. Second, we find a correlation of the membrane-thinning effect of these anesthetics with potency, consistent with our hypothesis and motivating further study. Finally, we aim to understand how anesthetics modulate their membrane reshaping effect in the presence of cholesterol in fusion pores.

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101 2026 Research Recognition Day