CM/BIO/ECE Seminar Series Presents: Krishna Sigdel

Wednesday, April 18, 2018 4:00pm

Physics Library, Room 223A, Physics Building

Departments: 

physics bldg

The MU Physics & Astronomy Department's Condensed Matter - Biological Physics - Electrical & Computer Engineering seminar series presents, "Mechanical Insights into Protein-Membrane Interactions via Atomic Force Microscopy," by postdoctoral fellow Krishna P. Sigdel, Physics & Astronomy, Wed., April 18, 4:00 p.m. Refreshments will be served beginning at 3:30 p.m.

Sigdel writes, "Understanding the interactions of proteins with the complex environment of cellular membranes is a longstanding and fundamental problem in biophysics. These interactions are important because they determine the three-dimensional structure and ultimately the function of membrane proteins, a large class of pharmaceutically relevant macromolecules that reside within cellular membranes. Conventional biochemical methods have been used to study protein-membrane interactions but elucidating mechanistic details from such assays has proven to be challenging. In this talk I will discuss a single-molecule approach to measure the interaction between a protein and a membrane. Distinct interaction patterns were observed between small proteins that differed only by a single monomer unit. These single-molecule measurements, together with analytical modeling and molecular dynamics simulations, provide a basis for improved understanding of the structural energetics of membrane proteins and their partitioning into the membrane. I will also discuss a project focused on the cancer-related membrane protein P-glycoprotein (P-gp) that plays a major role in human disease and drug disposition because of its ability to pump a chemically diverse range of drugs out of the cell. Deciphering the drug-induced conformational changes is key to understanding the molecular basis of transport and to developing novel pharmaceuticals. We directly imaged individual P-gp transporters reconstituted into a membrane and studied the protein structure and structural dynamics in physiological buffer solution. This work provides a foundation for future studies such as imaging the structural consequences of cancer drug binding to P-gp in near-native conditions."