Manipulation of Membrane Structure and Function Using Light
The 1st part of my presentation will focus on light triggered mechanistic investigation of membrane fusion using artificial caged SNAREs [Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor]. Membrane fusion is a fundamental process in life and plays a key role in exo- and endocytosis, fertilization, intracellular trafficking, enveloped virus infection, etc. All intracellular membrane fusion is directed by the formation of a specific complex of proteins, such as SNARE. Two SNARE proteins residing in the plasma membrane are syntaxin-1A (Sx) and SNAP-25. A SNARE protein residing in the membrane of synaptic vesicle is synaptobrevin (Syb). The SNAREs assemble into four-α-helix bundles. There are several mechanisms of SNARE mediated membrane fusion, but the exact nature of these processes is still unknown. I will demonstrate the design of artificial caged SNAREs using photolabile protecting groups to temporarily mask the functionality of the recognition site with the goal of obtaining deeper structural insights into the SNARE-mediated membrane fusion mechanism.
In the 2nd part of my presentation, I will illustrate how an understanding of membrane events can be used to promote drug molecules at tumor sites by passive and active targeting to tumor. Another goal is to target local pH of tumor site. A tumor microenvironment (cytosol) usually has a pH of 6.5-7.2, an endosomal pH of 5.0–6.0 and a lysosomal pH of 4.0−5.0, which is different from the normal tissues pH of 7.4. This pH gradient is of particular importance, since several drugs and carriers for cancer therapy are internalized through endocytosis and trapped within endosomal and lysosomal compartments. I will explain NIR pH switchable liposomal formulation where laser-induced photothermal heating is turned on at acidic pH (> 6.5) and turned off at physiological pH 7.4 which could show major toxic effects against tumors, without causing damage to normal cells. Drug release from thermosensitive liposome will be demonstrated using logical application of pH and photothermal heating. This liposomal formulation with laser could be a promising strategy for ‘Photothermal Cancer Theranostics’.