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Stressing Lipid Membranes: Effects of Polymers on Membrane Structural Integrity

Published online by Cambridge University Press:  02 January 2013

Jia-Yu Wang ,
Chi-Yuan Cheng ,
Ravinath. Kausik ,
Jaemin Chin ,
Songi. Han ,
Jeremy D. Marks  and
Ka Yee C. Lee
Jia-Yu Wang
Affiliation:
Department of Chemistry, Institute for Biophysical Dynamics & James Franck Institute, The University of Chicago, Illinois 60637, U.S.A
Chi-Yuan Cheng
Affiliation:
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, U.S.A.
Ravinath. Kausik
Affiliation:
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, U.S.A. Schlumberger-Doll Research, Cambridge, MA 02139, U.S.A.
Jaemin Chin
Affiliation:
Department of Chemistry, Institute for Biophysical Dynamics & James Franck Institute, The University of Chicago, Illinois 60637, U.S.A
Songi. Han
Affiliation:
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, U.S.A.
Jeremy D. Marks
Affiliation:
Department of Pediatrics, The University of Chicago, Illinois 60637, U.S.A.
Ka Yee C. Lee*
Affiliation:
Department of Chemistry, Institute for Biophysical Dynamics & James Franck Institute, The University of Chicago, Illinois 60637, U.S.A
*
*Email: [email protected]
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Abstract

Disruption of cell membranes triggers rapid metabolic energy exhaustion, then acute cellular necrosis. Cell membrane dysfunction due to loss of structure integrity is the pathology of tissue death in trauma, muscular dystrophies, reperfusion injuries and common diseases. It is now established that certain PEG-based biocompatible polymers, such as Poloxamer 188, Poloxamine 1107 and PEG, are effective in sealing of injured cell membranes, and thus can prevent acute necrosis if delivered within a few hours after injury. Despite these broad applications of PEG-based polymers for human health, the fundamental mechanisms of how PEG-based polymers interact with cell membranes are still under debate. Here, the effects of PEG-based biocompatible polymers on phospholipid membrane integrity under external stimuli (osmotic stress and oxidative stress) were explored using giant unilamellar vesicles (GUVs) as model cell membranes. Through fluorescence leakage assays and time-lapse fluorescence microscopy, we directly observed that the surface-adsorbed P188 can efficiently inhibits the loss of structural integrity of giant unilamellar vesicles (GUVs) under hypo-osmotic stress. We propose that the adsorption of polymers on the membrane surface is responsible for the cell membrane resealing process, while the insertion of the hydrophobic portion of the polymers increases membrane permeability. To elucidate the mechanism by which hydrophilic polymers help restore membrane integrity while their hydrophobic counterparts disrupt it, 1H Overhauser Dynamic Nuclear Polarization (ODNP)-NMR spectroscopy, a newly developed NMR technique that provides unprecedented resolution for differentiating weak surface adsorption versus translocation of polymers to membranes, was employed to sensitively detect polymer-lipid membrane interactions through the modulation of local hydration dynamics in lipid membranes. Our study shows that P188—the most hydrophilic poloxamer known as a membrane sealant—weakly adsorbs onto the membrane surface, yet effectively retards membrane hydration dynamics. Contrarily, P181—the most hydrophobic poloxamer known as a membrane permeabilizer—initially penetrates past lipid headgroups and enhances intrabilayer water diffusivity. Consequently, our results illustrate that the relative hydrophilic/hydrophobic ratio of the polymer dictates its functions. These findings gleaned from local hydration dynamics are well supported by our thermodynamics and fluorescence data.

Keywords

PolymerNMRoxidation
Type
Articles
Information
MRS Online Proceedings Library (OPL) , Volume 1480: Symposium S – Novel Characterization Methods for Biological Systems , 2012 , imrc12-1480-s2b-0012
Copyright
Copyright © Materials Research Society 2012 

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