Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

Mamontov, Eugene; Tyagi, M.; Qian, Shuo; Rai, Durgesh K.; Urban, Volker S.; Sharma, V. K.

doi:10.1021/acs.jpclett.6b01006

Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

Journal Article · Fri May 27 00:00:00 EDT 2016 · Journal of Physical Chemistry Letters

DOI:https://doi.org/10.1021/acs.jpclett.6b01006· OSTI ID:1259423

Mamontov, Eugene ^[1]; Tyagi, M. ^[2]; Qian, Shuo ^[1]; Rai, Durgesh K. ^[1]; Urban, Volker S. ^[1]; Sharma, V. K. ^[3]

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
National Institute of Standards and Technology Center for Neutron Research, Gaithersburg, MD (United States); Univ. of Maryland, College Park, MD (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bhabha Atomic Research Centre, Mumbai (India)

Here we discuss that the mechanism of action of antimicrobial peptides is traditionally attributed to the formation of pores in the lipid cell membranes of pathogens, which requires a substantial peptide to lipid ratio. However, using incoherent neutron scattering, we show that even at a concentration too low for pore formation, an archetypal antimicrobial peptide, melittin, disrupts the regular phase behavior of the microscopic dynamics in a phospholipid membrane, dimyristoylphosphatidylcholine (DMPC). At the same time, another antimicrobial peptide, alamethicin, does not exert a similar effect on the DMPC microscopic dynamics. The melittin-altered lateral motion of DMPC at physiological temperature no longer resembles the fluid-phase behavior characteristic of functional membranes of the living cells. The disruptive effect demonstrated by melittin even at low concentrations reveals a new mechanism of antimicrobial action relevant in more realistic scenarios, when peptide concentration is not as high as would be required for pore formation, which may facilitate treatment with antimicrobial peptides.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1259423

Journal Information:: Journal of Physical Chemistry Letters, Journal Name: Journal of Physical Chemistry Letters Vol. 7; ISSN 1948-7185

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (53)

Melittin: a Membrane-active Peptide with Diverse Functions Raghuraman, H.; Chattopadhyay, Amitabha Bioscience Reports, Vol. 27, Issue 4-5 https://doi.org/10.1007/s10540-006-9030-z	journal	August 2007
A restatement of melittin-induced effects on the thermotropism of zwitterionic phospholipids Dasseux, Jean-Louis; Faucon, Jean-François; Lafleur, Michael Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 775, Issue 1 https://doi.org/10.1016/0005-2736(84)90232-3	journal	August 1984
Morphological changes of phosphatidylcholine bilayers induced by melittin: vesicularization, fusion, discoidal particles Dufourcq, Jean; Faucon, Jean-Francois; Fourche, Georges Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 859, Issue 1 https://doi.org/10.1016/0005-2736(86)90315-9	journal	July 1986
The actions of melittin on membranes Dempsey, Christopher E. Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, Vol. 1031, Issue 2 https://doi.org/10.1016/0304-4157(90)90006-X	journal	May 1990
Differential scanning calorimetry and X-ray diffraction studies of the specificity of the interaction of antimicrobial peptides with membrane-mimetic systems Lohner, Karl; Prenner, Elmar J. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1462, Issue 1-2 https://doi.org/10.1016/S0005-2736(99)00204-7	journal	December 1999
A Model for the Lipid Pretransition: Coupling of Ripple Formation with the Chain-Melting Transition Heimburg, Thomas Biophysical Journal, Vol. 78, Issue 3 https://doi.org/10.1016/S0006-3495(00)76673-2	journal	March 2000
The Effect of Cholesterol on the Lateral Diffusion of Phospholipids in Oriented Bilayers Filippov, Andrey; Orädd, Greger; Lindblom, Göran Biophysical Journal, Vol. 84, Issue 5 https://doi.org/10.1016/S0006-3495(03)70033-2	journal	May 2003
Method of oriented circular dichroism Wu, Y.; Huang, H. W.; Olah, G. A. Biophysical Journal, Vol. 57, Issue 4 https://doi.org/10.1016/S0006-3495(90)82599-6	journal	April 1990
Ultrasonic study of melittin effects on phospholipid model membranes Colotto, A.; Kharakoz, D. P.; Lohner, K. Biophysical Journal, Vol. 65, Issue 6 https://doi.org/10.1016/S0006-3495(93)81298-0	journal	December 1993
Cooperative effects in the interaction between melittin and phosphatidylcholine model membranes. Studies by temperature scanning densitometry. Posch, M.; Rakusch, U.; Mollay, C. Journal of Biological Chemistry, Vol. 258, Issue 3 https://doi.org/10.1016/S0021-9258(18)33052-7	journal	February 1983
Molecular mechanism of antimicrobial peptides: The origin of cooperativity Huang, Huey W. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1758, Issue 9 https://doi.org/10.1016/j.bbamem.2006.02.001	journal	September 2006
Detergent-like actions of linear amphipathic cationic antimicrobial peptides Bechinger, Burkhard; Lohner, Karl Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1758, Issue 9 https://doi.org/10.1016/j.bbamem.2006.07.001	journal	September 2006
Alzheimer's disease amyloid-β peptide analogue alters the ps-dynamics of phospholipid membranes Buchsteiner, Alexandra; Hauβ, Thomas; Dante, Silvia Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 10 https://doi.org/10.1016/j.bbamem.2010.06.024	journal	October 2010
Peptide-induced bilayer thinning structure of unilamellar vesicles and the related binding behavior as revealed by X-ray scattering Su, Chun-Jen; Wu, Shiuan-Shiaou; Jeng, U-Ser Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1828, Issue 2 https://doi.org/10.1016/j.bbamem.2012.10.027	journal	February 2013
Melittin-induced cholesterol reorganization in lipid bilayer membranes Qian, Shuo; Heller, William T. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1848, Issue 10 https://doi.org/10.1016/j.bbamem.2015.06.012	journal	October 2015
Proline Facilitates Membrane Insertion of the Antimicrobial Peptide Maculatin 1.1 via Surface Indentation and Subsequent Lipid Disordering Fernandez, David I.; Lee, Tzong-Hsien; Sani, Marc-Antoine Biophysical Journal, Vol. 104, Issue 7 https://doi.org/10.1016/j.bpj.2013.01.059	journal	April 2013
Antimicrobial peptide alamethicin insertion into lipid bilayer: A QCM-D exploration Wang, Kathleen F.; Nagarajan, Ramanathan; Camesano, Terri A. Colloids and Surfaces B: Biointerfaces, Vol. 116 https://doi.org/10.1016/j.colsurfb.2014.01.036	journal	April 2014
Role of lipids in the interaction of antimicrobial peptides with membranes Teixeira, Vitor; Feio, Maria J.; Bastos, Margarida Progress in Lipid Research, Vol. 51, Issue 2 https://doi.org/10.1016/j.plipres.2011.12.005	journal	April 2012
Structure and Dynamics of Ionic Micelles: MD Simulation and Neutron Scattering Study Aoun, B.; Sharma, V. K.; Pellegrini, E. The Journal of Physical Chemistry B, Vol. 119, Issue 15 https://doi.org/10.1021/acs.jpcb.5b00020	journal	April 2015
Nanoscopic Dynamics of Phospholipid in Unilamellar Vesicles: Effect of Gel to Fluid Phase Transition Sharma, V. K.; Mamontov, E.; Anunciado, D. B. The Journal of Physical Chemistry B, Vol. 119, Issue 12 https://doi.org/10.1021/acs.jpcb.5b00220	journal	March 2015
Effect of α-Tocopherol on the Microscopic Dynamics of Dimyristoylphosphatidylcholine Membrane Sharma, V. K.; Mamontov, E.; Tyagi, M. The Journal of Physical Chemistry B, Vol. 120, Issue 1 https://doi.org/10.1021/acs.jpcb.5b10417	journal	December 2015
Antimicrobial Peptide Pores in Membranes Detected by Neutron In-Plane Scattering He, Ke; Ludtke, Steve J.; Huang, Huey W. Biochemistry, Vol. 34, Issue 48 https://doi.org/10.1021/bi00048a002	journal	December 1995
Action of Antimicrobial Peptides: Two-State Model ^† Huang, Huey W. Biochemistry, Vol. 39, Issue 29 https://doi.org/10.1021/bi000946l	journal	July 2000
Lateral diffusion in the liquid phases of dimyristoylphosphatidylcholine/cholesterol lipid bilayers: a free volume analysis Almeida, Paulo F. F.; Vaz, Winchil L. C.; Thompson, T. E. Biochemistry, Vol. 31, Issue 29 https://doi.org/10.1021/bi00144a013	journal	July 1992
Energetics of Pore Formation Induced by Membrane Active Peptides ^† Lee, Ming-Tao; Chen, Fang-Yu; Huang, Huey W. Biochemistry, Vol. 43, Issue 12 https://doi.org/10.1021/bi036153r	journal	March 2004
Molecular Mechanism of Long-Range Diffusion in Phospholipid Membranes Studied by Quasielastic Neutron Scattering Busch, Sebastian; Smuda, Christoph; Pardo, Luis Carlos Journal of the American Chemical Society, Vol. 132, Issue 10 https://doi.org/10.1021/ja907581s	journal	March 2010
Internal Dynamics in SDS Micelles: Neutron Scattering Study Sharma, V. K.; Mitra, S.; Verma, G. The Journal of Physical Chemistry B, Vol. 114, Issue 51 https://doi.org/10.1021/jp108274y	journal	December 2010
Peptide-Induced Asymmetric Distribution of Charged Lipids in a Vesicle Bilayer Revealed by Small-Angle Neutron Scattering Qian, Shuo; Heller, William T. The Journal of Physical Chemistry B, Vol. 115, Issue 32 https://doi.org/10.1021/jp204045t	journal	August 2011
Dynamical Features in Cationic Micelles of Varied Chain Length Sharma, V. K.; Mitra, S.; Sakai, V. Garcia The Journal of Physical Chemistry B, Vol. 116, Issue 30 https://doi.org/10.1021/jp304841a	journal	July 2012
Dynamics in Anionic Micelles: Effect of Phenyl Ring Sharma, V. K.; Mitra, S.; Johnson, M. The Journal of Physical Chemistry B, Vol. 117, Issue 20 https://doi.org/10.1021/jp401831y	journal	May 2013
Alamethicin Disrupts the Cholesterol Distribution in Dimyristoyl Phosphatidylcholine–Cholesterol Lipid Bilayers Qian, Shuo; Rai, Durgesh; Heller, William T. The Journal of Physical Chemistry B, Vol. 118, Issue 38 https://doi.org/10.1021/jp504886u	journal	September 2014
Antimicrobial peptides of multicellular organisms Zasloff, Michael Nature, Vol. 415, Issue 6870 https://doi.org/10.1038/415389a	journal	January 2002
Membranes are more mosaic than fluid Engelman, Donald M. Nature, Vol. 438, Issue 7068 https://doi.org/10.1038/nature04394	journal	November 2005
Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Brogden, Kim A. Nature Reviews Microbiology, Vol. 3, Issue 3 https://doi.org/10.1038/nrmicro1098	journal	March 2005
Can innate immunity be enhanced to treat microbial infections? Finlay, B. Brett; Hancock, Robert E. W. Nature Reviews Microbiology, Vol. 2, Issue 6 https://doi.org/10.1038/nrmicro908	journal	June 2004
Effect of antimicrobial peptide on the dynamics of phosphocholine membrane: role of cholesterol and physical state of bilayer Sharma, V. K.; Mamontov, E.; Anunciado, D. B. Soft Matter, Vol. 11, Issue 34 https://doi.org/10.1039/C5SM01562F	journal	January 2015
Diffusion in single supported lipid bilayers studied by quasi-elastic neutron scattering Armstrong, Clare L.; Kaye, Martin D.; Zamponi, Michaela Soft Matter, Vol. 6, Issue 23 https://doi.org/10.1039/c0sm00637h	journal	January 2010
Conformational and segmental dynamics in lipid-based vesicles Gerelli, Yuri; Sakai, Victoria García; Ollivier, Jacques Soft Matter, Vol. 7, Issue 8 https://doi.org/10.1039/c0sm01301c	journal	January 2011
Short range ballistic motion in fluid lipid bilayers studied by quasi-elastic neutron scattering Armstrong, C. L.; Trapp, M.; Peters, J. Soft Matter, Vol. 7, Issue 18 https://doi.org/10.1039/c1sm05691c	journal	January 2011
The picosecond dynamics of the phospholipid dimyristoylphosphatidylcholine in mono- and bilayers Busch, Sebastian; Pardo, Luis Carlos; Smuda, Christoph Soft Matter, Vol. 8, Issue 13 https://doi.org/10.1039/c2sm07380c	journal	January 2012
The dynamical landscape in CTAB micelles Sharma, V. K.; Mitra, S.; Garcia Sakai, V. Soft Matter, Vol. 8, Issue 27 https://doi.org/10.1039/c2sm25515d	journal	January 2012
Partitioning of ethanol into lipid membranes and its effect on fluidity and permeability as seen by X-ray and neutron scattering Toppozini, Laura; Armstrong, Clare L.; Barrett, Matthew A. Soft Matter, Vol. 8, Issue 47 https://doi.org/10.1039/c2sm26546j	journal	January 2012
High hydrostatic pressure effects investigated by neutron scattering on lipid multilamellar vesicles Trapp, Marcus; Marion, Jérémie; Tehei, Moeava Physical Chemistry Chemical Physics, Vol. 15, Issue 48 https://doi.org/10.1039/c3cp52762j	journal	January 2013
The high-flux backscattering spectrometer at the NIST Center for Neutron Research Meyer, A.; Dimeo, R. M.; Gehring, P. M. Review of Scientific Instruments, Vol. 74, Issue 5 https://doi.org/10.1063/1.1568557	journal	May 2003
Self-diffusion in molecular liquids: Medium-chain n-alkanes and coenzyme Q10 studied by quasielastic neutron scattering Smuda, Christoph; Busch, Sebastian; Gemmecker, Gerd The Journal of Chemical Physics, Vol. 129, Issue 1 https://doi.org/10.1063/1.2943673	journal	July 2008
A time-of-flight backscattering spectrometer at the Spallation Neutron Source, BASIS Mamontov, E.; Herwig, K. W. Review of Scientific Instruments, Vol. 82, Issue 8 https://doi.org/10.1063/1.3626214	journal	August 2011
Process of inducing pores in membranes by melittin Lee, M. -T.; Sun, T. -L.; Hung, W. -C. Proceedings of the National Academy of Sciences, Vol. 110, Issue 35 https://doi.org/10.1073/pnas.1307010110	journal	August 2013
The Bio-SANS instrument at the High Flux Isotope Reactor of Oak Ridge National Laboratory Heller, William T.; Urban, Volker S.; Lynn, Gary W. Journal of Applied Crystallography, Vol. 47, Issue 4 https://doi.org/10.1107/S1600576714011285	journal	June 2014
Alamethicin: A Peptide Model for Voltage Gating and Protein-Membrane Interactions Cafiso, D. S. Annual Review of Biophysics and Biomolecular Structure, Vol. 23, Issue 1 https://doi.org/10.1146/annurev.bb.23.060194.001041	journal	June 1994
NMR Studies of Lipid Lateral Diffusion in the DMPC/Gramicidin D/Water System: Peptide Aggregation and Obstruction Effects Orädd, Greger; Lindblom, Göran Biophysical Journal, Vol. 87, Issue 2 https://doi.org/10.1529/biophysj.103.038828	journal	August 2004
Morphological Behavior of Lipid Bilayers Induced by Melittin near the Phase Transition Temperature Toraya, Shuichi; Nagao, Takashi; Norisada, Kazushi Biophysical Journal, Vol. 89, Issue 5 https://doi.org/10.1529/biophysj.105.059311	journal	November 2005
Structure of the Alamethicin Pore Reconstructed by X-Ray Diffraction Analysis Qian, Shuo; Wang, Wangchen; Yang, Lin Biophysical Journal, Vol. 94, Issue 9 https://doi.org/10.1529/biophysj.107.126474	journal	May 2008
DAVE: A Comprehensive Software Suite for the Reduction, Visualization, and Analysis of Low Energy Neutron Spectroscopic Data Azuah, Richard Tumanjong; Kneller, Larry R.; Qiu, Yiming Journal of Research of the National Institute of Standards and Technology, Vol. 114, Issue 6 https://doi.org/10.6028/jres.114.025	journal	November 2009

Cited By (5)

Effect of Bifunctional β Defensin 2-Modified Scaffold on Bone Defect Reconstruction Peng, Yiyu; Li, Lunhao; Yuan, Qingyue ACS Omega, Vol. 5, Issue 8 https://doi.org/10.1021/acsomega.9b04249	journal	February 2020
Dynamical Transitions and Diffusion Mechanism in DODAB Bilayer Dubey, P. S.; Srinivasan, H.; Sharma, V. K. Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-19899-6	journal	January 2018
Deciphering interactions of ionic liquids with biomembrane Sharma, V. K.; Mukhopadhyay, R. Biophysical Reviews, Vol. 10, Issue 3 https://doi.org/10.1007/s12551-018-0410-y	journal	March 2018
Relaxation dynamics of saturated and unsaturated oriented lipid bilayers Nanda, Hirsh; García Sakai, Victoria; Khodadadi, Sheila Soft Matter, Vol. 14, Issue 29 https://doi.org/10.1039/c7sm01720k	journal	January 2018
Membrane softening by nonsteroidal anti-inflammatory drugs investigated by neutron spin echo Sharma, V. K.; Nagao, M.; Rai, D. K. Physical Chemistry Chemical Physics, Vol. 21, Issue 36 https://doi.org/10.1039/c9cp03767e	journal	January 2019

Similar Records

Asymmetric distribution of charged lipids between the leaflets of a vesicle bilayer induced by melittin and alamethicin

Journal Article · Fri Dec 31 23:00:00 EST 2010 · Journal of Physical Chemistry B · OSTI ID:1021973

Effect of antimicrobial peptide on dynamics of phosphocholine membrane: role of cholesterol and physical state of bilayer

Journal Article · Tue Jun 23 20:00:00 EDT 2015 · Soft Matter · OSTI ID:1214022

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
alamethicin
antimicrobial peptides
dynamics
melittin
membrane-peptide interactions
neutron scattering
phosphocholine membrane

Dynamical and phase behavior of a phospholipid membrane altered by an antimicrobial peptide at low concentration

Citation Formats

References (53)

Cited By (5)

Similar Records

Related Subjects