Physics Colloquium, "The pH Low Insertion Peptides (pHLIPs): Mechanism of Insertion and Medical Applications ," by Oleg A. Andreev, Associate Professor, Physics Department, University of Rhode Island
Science / Technology - Colloquium
Monday, April 30, 2012
4:00 PM-5:00 PM
The pH Low Insertion Peptides (pHLIPs) are membrane peptides that insert in membrane at low pH (<7.0) and do not at physiological (7.4) or higher pH. We investigated mechanism of insertion of pHLIP and found that protonation of Asp residues increases the hydrophobicity of peptide and triggers insertion and formation of transmembrane helix. Insertion of pHLIP is accompanied with significant changes in tryptophan fluorescence and CD spectra. We found that after drop of pH a helix is formed first and then transmembrane configuration is adopted with the C-terminus is inside of liposome or cell and the N-terminus staying outside a membrane. Since the affinity of pHLIP to membrane is higher at low pH we came to an idea to use pHLIP to target acidic diseased tissue in vivo. It is well known that solid tumors develop an acidic extracellular environment due to shift of cancer cells to glycolytic pathway of energy production (Warburg effect). Indeed, we proved that pHLIP labeled with various imaging agents can find and stained primary tumors and metastatic lesions of even very small sizes. pHLIP can be used as a tumor targeting agent and it can deliver small molecules, nanoparticles and liposomes to tumors in vivo. Since the C-terminus of pHLIP inserts across membrane it can translocate cell impermeable molecules into cytoplasm acting as a single-molecular transporter or nanosyringe. We demonstrated that pHLIP can translocate several biologically functional molecules across a membrane and release them inside cells. The ability of pHLIP to find cancer cells and translocate molecules across membrane opens new opportunity for targeted cancer therapy. pHLIP represents a novel class of theranostic agents for imaging and treatment of tumors.
Refreshments will be served in Olin Hall 118 at 3:30 P.M.
Sponsored by: WPI Physics Department, Dr. Qi Wen
Suggested Audiences: College
Last Modified: April 10, 2012 at 9:30 AM