Phospholipid Head Groups and Interactions with Transition Metal Ions

Restricted (Penn State Only)
Author:
Sendecki, Anne M
Graduate Program:
Chemistry
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
June 14, 2017
Committee Members:
  • Paul S Cremer, Dissertation Advisor
  • Paul S Cremer, Committee Chair
  • Christine Dolan Keating, Committee Member
  • Alexey Silakov, Committee Member
  • Peter J Butler, Outside Member
Keywords:
  • Supported Lipid Bilayers
  • Phosphatidylethanolamine
  • Fluorescence Recovery after Photobleaching
  • Transition metal ion binding
  • Lipid domains
  • Small molecule chemotaxis
  • Phosphatidylserine
Abstract:
Herein, the biophysical properties of lipid head groups is explored, with a focus on the effects of specific binding of transition metal ions Ni2+, Cu2+, and Zn2+. First, we incorporate high amounts of phosphatidylethanolamine (PE) into supported lipid bilayers (SLBs), which has proven historically difficult. Under certain conditions, interesting phase behavior such as domains formed from two-component systems or three-dimensional tubules are observed. Then, binding of Ni2+ and Cu2+ to deprotonated amines in the PE head groups is measured in microfluidic devices by fluorescence quenching. As copper is redox active, the effect of Cu2+-PE on the oxidation of membrane species is explored, which could be important for neurodegenerative diseases. Next, we hypothesized that metal ion complexes with phosphatidylserine (PS) would disrupt domain formation. PS is a negatively charged lipid and has been shown to have tight binding with Cu2+ that does not change the net charge on the membrane, while Zn2+ interacts electrostatically with the phosphate and carboxylate moieties. While binding of Cu2+ seems to have no effect on PS domains, high concentration of Zn2+ appears to stabilize the domains. Another objective of this work was to clarify the mechanism of molecular chemotaxis to direct the motion of bulk lipid vesicles. These results suggest the roles of lipid head groups are diverse and varied, and are compounded by interactions with divalent transition metal ions.