Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations

Haden L. Scott; Violeta Burns-Casamayor; Andrew C. Dixson; Robert F. Standaert; Christopher B. Stanley; Laura Roxana Stingaciu; Jan Michael Y. Carrillo; Bobby G. Sumpter; John Katsaras; Wei Qiang; Frederick A. Heberle; Blake Mertz; Rana Ashkar; Francisco N. Barrera

doi:10.1016/j.bbamem.2024.184349

Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations

Haden L. Scott, Violeta Burns-Casamayor, Andrew C. Dixson, Robert F. Standaert, Christopher B. Stanley, Laura Roxana Stingaciu, Jan Michael Y. Carrillo, Bobby G. Sumpter, John Katsaras, Wei Qiang, Frederick A. Heberle, Blake Mertz, Rana Ashkar, Francisco N. Barrera

Research output: Contribution to journal › Article › peer-review

Abstract

Cell membranes are responsible for a range of biological processes that require interactions between lipids and proteins. While the effects of lipids on proteins are becoming better understood, our knowledge of how protein conformational changes influence membrane dynamics remains rudimentary. Here, we performed experiments and computer simulations to study the dynamic response of a lipid membrane to changes in the conformational state of pH-low insertion peptide (pHLIP), which transitions from a surface-associated (SA) state at neutral or basic pH to a transmembrane (TM) α-helix under acidic conditions. Our results show that TM-pHLIP significantly slows down membrane thickness fluctuations due to an increase in effective membrane viscosity. Our findings suggest a possible membrane regulatory mechanism, where the TM helix affects lipid chain conformations, and subsequently alters membrane fluctuations and viscosity.

Original language	English
Article number	184349
Journal	Biochimica et Biophysica Acta - Biomembranes
Volume	1866
Issue number	7
DOIs	https://doi.org/10.1016/j.bbamem.2024.184349
State	Published - Oct 2024

Funding

The authors thank Dr. Michihiro Nagao, Dr. Elizabeth G. Kelley, and Dr. Piotr Zolnierczuk for technical assistance and useful discussions of NSE experiments. We thank Vanessa P. Nguyen and Justin M. Westerfield for comments on the manuscript. This work was partially supported by grant R35GM140846 from the NIH (F.N.B.), NSF grant No. MCB-1817929 (F.A.H.), NSF grant No. MCB-2137154 (R.A.), and by funds from the UT-ORNL Joint Institute for Biological Sciences (JIBS) to F.N.B. Support was also received from the UTK-ORNL Science Alliance in the form of a Joint Directed Research and Development Award (to F.N.B.). W.Q. was supported by NIH grant R01GM125853 and SUNY Binghamton. J.K. was supported through the Scientific User Facilities Division of the Department of Energy (DOE) Office of Science, sponsored by the Basic Energy Science (BES) Program, DOE Office of Science, under Contract No. DEAC05-00OR22725. Sample preparation and characterization were supported by the Biophysical Characterization Laboratory suite of the Shull Wollan Center at ORNL. Access to the NG3-30m SANS and NGA-NSE was provided by the Center for High Resolution Neutron Scattering, a partnership between the National Institute of Standards and Technology and the National Science Foundation under agreement no. DMR-1508249. Research conducted at ORNL's Spallation Neutron Source was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy. Oak Ridge National Laboratory is managed by UT-Battelle, LLC under US DOE Contract No. DE-AC05-00OR22725. The coarse-grained molecular dynamics simulations and associated computational research were supported by the Center for Nanophase Materials Sciences, a US DOE Office of Science User Facility at Oak Ridge National Laboratory. This study used resources of the Oak Ridge Leadership Computing Facility at Oak Ridge National Laboratory. Note. Any mention of commercial products is for information only; it does not imply recommendation or endorsement by NIST. The authors thank Dr. Michihiro Nagao, Dr. Elizabeth G. Kelley, and Dr. Piotr Zolnierczuk for technical assistance and useful discussions of NSE experiments. We thank Vanessa P. Nguyen and Justin M. Westerfield for comments on the manuscript. This work was partially supported by grant R35GM140846 from the NIH (F.N.B.), NSF grant No. MCB-1817929 (F.A.H.), NSF grant No. MCB-2137154 (R.A.), and by funds from the UT-ORNL Joint Institute for Biological Sciences (JIBS) to F.N.B. Support was also received from the UTK-ORNL Science Alliance in the form of a Joint Directed Research and Development Award (to F.N.B.). W.Q. was supported by NIH grant R01GM125853 and SUNY Binghamton . J.K. was supported through the Scientific User Facilities Division of the Department of Energy (DOE) Office of Science , sponsored by the Basic Energy Science (BES) Program, DOE Office of Science , under Contract No. DEAC05-00OR22725 . Sample preparation and characterization were supported by the Biophysical Characterization Laboratory suite of the Shull Wollan Center at ORNL. Access to the NG3-30m SANS and NGA-NSE was provided by the Center for High Resolution Neutron Scattering, a partnership between the National Institute of Standards and Technology and the National Science Foundation under agreement no. DMR-1508249. Research conducted at ORNL's Spallation Neutron Source was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy . Oak Ridge National Laboratory is managed by UT-Battelle, LLC under US DOE Contract No. DE-AC05-00OR22725 . The coarse-grained molecular dynamics simulations and associated computational research were supported by the Center for Nanophase Materials Sciences, a US DOE Office of Science User Facility at Oak Ridge National Laboratory . This study used resources of the Oak Ridge Leadership Computing Facility at Oak Ridge National Laboratory.

Keywords

Lipid-protein interactions
MD simulations
Membrane dynamics
Membrane viscosity

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10.1016/j.bbamem.2024.184349

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Scott, H. L., Burns-Casamayor, V., Dixson, A. C., Standaert, R. F., Stanley, C. B., Stingaciu, L. R., Carrillo, J. M. Y., Sumpter, B. G., Katsaras, J., Qiang, W., Heberle, F. A., Mertz, B., Ashkar, R., & Barrera, F. N. (2024). Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations. Biochimica et Biophysica Acta - Biomembranes, 1866(7), Article 184349. https://doi.org/10.1016/j.bbamem.2024.184349

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title = "Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations",

abstract = "Cell membranes are responsible for a range of biological processes that require interactions between lipids and proteins. While the effects of lipids on proteins are becoming better understood, our knowledge of how protein conformational changes influence membrane dynamics remains rudimentary. Here, we performed experiments and computer simulations to study the dynamic response of a lipid membrane to changes in the conformational state of pH-low insertion peptide (pHLIP), which transitions from a surface-associated (SA) state at neutral or basic pH to a transmembrane (TM) α-helix under acidic conditions. Our results show that TM-pHLIP significantly slows down membrane thickness fluctuations due to an increase in effective membrane viscosity. Our findings suggest a possible membrane regulatory mechanism, where the TM helix affects lipid chain conformations, and subsequently alters membrane fluctuations and viscosity.",

keywords = "Lipid-protein interactions, MD simulations, Membrane dynamics, Membrane viscosity",

author = "Scott, \{Haden L.\} and Violeta Burns-Casamayor and Dixson, \{Andrew C.\} and Standaert, \{Robert F.\} and Stanley, \{Christopher B.\} and Stingaciu, \{Laura Roxana\} and Carrillo, \{Jan Michael Y.\} and Sumpter, \{Bobby G.\} and John Katsaras and Wei Qiang and Heberle, \{Frederick A.\} and Blake Mertz and Rana Ashkar and Barrera, \{Francisco N.\}",

note = "Publisher Copyright: {\textcopyright} 2024 Elsevier B.V.",

year = "2024",

month = oct,

doi = "10.1016/j.bbamem.2024.184349",

language = "English",

volume = "1866",

journal = "Biochimica et Biophysica Acta - Biomembranes",

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Scott, HL, Burns-Casamayor, V, Dixson, AC, Standaert, RF, Stanley, CB , Stingaciu, LR , Carrillo, JMY, Sumpter, BG, Katsaras, J, Qiang, W, Heberle, FA, Mertz, B, Ashkar, R & Barrera, FN 2024, 'Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations', Biochimica et Biophysica Acta - Biomembranes, vol. 1866, no. 7, 184349. https://doi.org/10.1016/j.bbamem.2024.184349

TY - JOUR

T1 - Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations

AU - Scott, Haden L.

AU - Burns-Casamayor, Violeta

AU - Dixson, Andrew C.

AU - Standaert, Robert F.

AU - Stanley, Christopher B.

AU - Stingaciu, Laura Roxana

AU - Carrillo, Jan Michael Y.

AU - Sumpter, Bobby G.

AU - Katsaras, John

AU - Qiang, Wei

AU - Heberle, Frederick A.

AU - Mertz, Blake

AU - Ashkar, Rana

AU - Barrera, Francisco N.

PY - 2024/10

Y1 - 2024/10

N2 - Cell membranes are responsible for a range of biological processes that require interactions between lipids and proteins. While the effects of lipids on proteins are becoming better understood, our knowledge of how protein conformational changes influence membrane dynamics remains rudimentary. Here, we performed experiments and computer simulations to study the dynamic response of a lipid membrane to changes in the conformational state of pH-low insertion peptide (pHLIP), which transitions from a surface-associated (SA) state at neutral or basic pH to a transmembrane (TM) α-helix under acidic conditions. Our results show that TM-pHLIP significantly slows down membrane thickness fluctuations due to an increase in effective membrane viscosity. Our findings suggest a possible membrane regulatory mechanism, where the TM helix affects lipid chain conformations, and subsequently alters membrane fluctuations and viscosity.

AB - Cell membranes are responsible for a range of biological processes that require interactions between lipids and proteins. While the effects of lipids on proteins are becoming better understood, our knowledge of how protein conformational changes influence membrane dynamics remains rudimentary. Here, we performed experiments and computer simulations to study the dynamic response of a lipid membrane to changes in the conformational state of pH-low insertion peptide (pHLIP), which transitions from a surface-associated (SA) state at neutral or basic pH to a transmembrane (TM) α-helix under acidic conditions. Our results show that TM-pHLIP significantly slows down membrane thickness fluctuations due to an increase in effective membrane viscosity. Our findings suggest a possible membrane regulatory mechanism, where the TM helix affects lipid chain conformations, and subsequently alters membrane fluctuations and viscosity.

KW - Lipid-protein interactions

KW - MD simulations

KW - Membrane dynamics

KW - Membrane viscosity

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IS - 7

M1 - 184349

ER -

Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations

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