Modulation of Cu 2+ Binding to Sphingosine-1-Phosphate by Lipid Charge

Alexis J. Baxter, Adriana N. Santiago-Ruiz, Tinglu Yang, Paul S. Cremer

Research output: Contribution to journalArticle

Abstract

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that is thought to participate in the regulation of many physiological processes and may play a key role in several diseases. Herein, we found that Cu 2+ binds tightly to supported lipid bilayers (SLBs) containing S1P. Specifically, we demonstrated via fluorescence assays that Cu 2+ -S1P binding was bivalent and sensitive to the concentration of S1P in the SLB. In fact, the apparent equilibrium dissociation constant, K DApp , tightened by a factor of 132 from 4.5 μM to 34 nM as the S1P density was increased from 5.0 to 20 mol %. A major driving force for this apparent tightening was the more negative surface potential with increasing S1P concentration. This potential remained unaltered upon Cu 2+ binding at pH 7.4 because two protons were released for every Cu 2+ that bound. At pH 5.4, however, Cu 2+ could not outcompete protons for the amine and no binding occurred. Moreover, at pH 9.4, the amine was partially deprotonated before Cu 2+ binding and the surface potential became more positive on binding. The results for Cu 2+ -S1P binding were reminiscent of those for Cu 2+ -phosphatidylserine binding, where a carboxylate group helped to deprotonate the amine. In the case of S1P, however, the phosphate needed to bear two negative charges to facilitate amine deprotonation in the presence of Cu 2+ .

Original languageEnglish (US)
Pages (from-to)824-830
Number of pages7
JournalLangmuir
Volume35
Issue number3
DOIs
StatePublished - Jan 22 2019

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry

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