Undergraduate students in the Stokes lab analyze biologically- and environmentally-relevant interfaces, particularly the lipid-aqueous interface. In addition to learning to use the laser spectroscopy method second harmonic generation (SHG), students in our lab also learn to use a myriad of bioanalytical techniques and surface analysis tools including atomic force microscopy (AFM), contact angle goniometry, circular dichroism (CD), UV-Vis spectroscopy, attenuated total reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy, fluorescence microscopy, and dynamic light scattering (DLS). Here are two current projects we are working on:
1) Adsorption of antipsychotics to integral membrane receptors
We are studying two small-molecule drugs, clozapine and chlorpromazine, which are similar in size and hydrophobicity, but differ in shape, charge, and electronic properties. Both drugs target membrane-bound receptors in the brain and are FDA-approved to treat schizophrenia. Using second harmonic generation, a laser-based spectroscopy, we directly quantify adsorption of both clozapine and chlorpromazine to artificial membranes, called supported lipid bilayers. These membranes are composed of phospholipids which mimic the lipids found in the plasma membrane of human brain cells. Drug-membrane receptor interactions are difficult to study and model in vitro because proteins denature and unfold in aqueous solution, and can aggregate and form microdomains in lipid phases. We aim to differentiate between drug-lipid and drug-protein interactions. Our studies will provide a molecular-level, quantitative description of how antipsychotic drugs such as clozapine and chlorpromazine bind to transmembrane proteins such as the serotonin and dopamine receptors.
2) A predictive model describing how water-soluble peptoids adsorb to lipid bilayers
Given the promising applications of peptoid-based therapies, a molecular-level understanding of how peptoids interact with phospholipids—a major component of cell plasma membranes—is very important and will allow us predict how peptoids will behave in the human body. We quantified binding of 3- and 15-residue water-soluble peptoids adsorbed to phospholipids of varying compositions. We aim to generalize these studies and provide a predictive model describing peptoid sequence features that contribute to their interactions with lipids.