PhD thesis supervisor: dr. Martynas Talaikis (apply for recommendation)
Investigation of s100 protein-induced neuronal membrane disruption via vibrational spectroscopic techniques
During Alzheimer’s, Parkinson’s, and other neurodegenerative disorders, inflammatory proteins can perturb the structural organization of neuronal plasma membranes, compromising barrier function, ion homeostasis, and membrane-associated signaling, and thereby contributing to progressive neuronal dysfunction and death. Accumulating evidence indicates that S100 family proteins participate in these pathological cascades by binding to lipid interfaces, reorganizing membrane domains, and facilitating membrane damage under pro-inflammatory conditions, ultimately accelerating neurodegenerative progression. The aim of this work is to systematically investigate interactions of S100 family proteins with model neuronal plasma membranes under strictly controlled conditions at an electrochemical interface, where membrane composition and interfacial potential can be tuned with high precision. We will employ surface-enhanced infrared absorption spectroscopy (SEIRAS) and sum-frequency generation (SFG) spectroscopy, two interface-selective vibrational methods with high sensitivity and molecular specificity to conformational changes and intermolecular interactions at phase boundaries. By correlating spectral markers of lipid order and protein binding with electrochemical control parameters, these studies will elucidate mechanistic pathways by which S100 proteins induce membrane perturbation and damage, and will inform more rational strategies for therapeutic intervention.