Kathryn Saulcy BIOC430 S17
Chemistry/Biochemistry Research 430
- Spring 2017
- Kate Saulcy
- Sophomore Biochemistry Major
Research Times
Tuesday ~6/7 to 9/10pm
- section 01 = 0.25 credit = 4 hours per week.
Proposed Research Project
Insulin: It's Structure, Function, and Interaction in Model Cell Membranes
General Information
- Advisor: Audra Sostarecz
- Other research student collaborators: none
- Other Research Collaborators: Dr. Debbie C. Crans (Colorado State University)
Proposal
- Insulin is a polypeptide hormone that is created and used by a healthy human body to regulate blood sugar. The specific conformation that an insulin molecule adopts affects the stability and functionality of the hormone. Interactions with lipids, specifically Dipalmitoylphosphatidylcholine (DPPC) causes conformational changes in the shape of the insulin molecule and its state of aggregation. The Langmuir technique can be used to create monolayers of insulin, both human recombinant and bovine. Samples of insulin were mixed with lipid, at varying ratios, to determine any molecular interactions between the two compounds and to determine to what extent they interact. At a 25% Insulin/75% DPPC ratio, insulin makes a monolayer of DPPC more fluid. At a 75% Insulin/25% DPPC ratio, DPPC orders the insulin molecules. Subcutaneous injection exposes insulin molecules to lipid and this interaction appears, due to the disappearance of a phase transition on the mixed isotherm, to cause the insulin molecules to adopt a hexameric conformation. As the most active form of insulin is the monomer, this may account for less effective or incorrect dosing of insulin.
In the presence of zinc, insulin is known to bind into hexamers. This is how long-acting medical insulin is stored. The Langmuir technique, with a multi-well plate, can be used to investigate changes in pressure that correspond with changes in molecular area. These changes indicate a conformational change in the insulin molecule and thus a change in effectiveness within the human body.
Instruments to be used
- Langmuir monolayer trough
References (2 minimum)
http://pubs.acs.org/doi/full/10.1021/la204201w?src=recsys http://pubs.acs.org/doi/abs/10.1021/jp3046643
(more available upon request)
Research pledge
I, Kate Saulcy, have read the Chem/Bioc 430 course syllabus and understand the general structure and expectations of the research program. The above material was prepared after consultation, and in conjunction with my research advisor.