The University of Southampton
University of Southampton Institutional Repository

Headgroup structure and cation binding in phosphatidylserine lipid bilayers

Headgroup structure and cation binding in phosphatidylserine lipid bilayers
Headgroup structure and cation binding in phosphatidylserine lipid bilayers

Phosphatidylserine (PS) is a negatively charged lipid type commonly found in eukaryotic membranes, where it interacts with proteins via nonspecific electrostatic interactions as well as via specific binding. Moreover, in the presence of calcium ions, PS lipids can induce membrane fusion and phase separation. Molecular details of these phenomena remain poorly understood, partly because accurate models to interpret the experimental data have not been available. Here we gather a set of previously published experimental NMR data of C-H bond order parameter magnitudes, |SCH|, for pure PS and mixed PS:PC (phosphatidylcholine) lipid bilayers and augment this data set by measuring the signs of SCH in the PS headgroup using S-DROSS solid-state NMR spectroscopy. The augmented data set is then used to assess the accuracy of the PS headgroup structures in, and the cation binding to, PS-containing membranes in the most commonly used classical molecular dynamics (MD) force fields including CHARMM36, Lipid17, MacRog, Slipids, GROMOS-CKP, Berger, and variants. We show large discrepancies between different force fields and that none of them reproduces the NMR data within experimental accuracy. However, the best MD models can detect the most essential differences between PC and PS headgroup structures. The cation binding affinity is not captured correctly by any of the PS force fields - an observation that is in line with our previous results for PC lipids. Moreover, the simulated response of the PS headgroup to bound ions can differ from experiments even qualitatively. The collected experimental data set and simulation results will pave the way for development of lipid force fields that correctly describe the biologically relevant negatively charged membranes and their interactions with ions. This work is part of the NMRlipids open collaboration project (nmrlipids.blogspot.fi).

1520-6106
9066-9079
Antila, Hanne
0d3b66cc-5267-48e9-99c3-b4fd3d33979c
Buslaev, Pavel
6c4fef87-961e-4a1a-8af9-011834808c37
Favela-Rosales, Fernando
e94ff5ca-f524-4613-92d6-fa4e895df6d9
Ferreira, Tiago M.
6cb97ad9-84f2-43f0-ab04-f18f2403d69c
Gushchin, Ivan
b14ee732-a1a4-46c7-8cb5-1850b65653f0
Javanainen, Matti
56eca9a4-6434-43b0-8e1c-ef294ff46404
Kav, Batuhan
1cc1a69d-d447-4ece-bc5b-264943e97053
Madsen, Jesper J.
b1ec873c-57bb-4b10-9d8d-2a6ed2ce99da
Melcr, Josef
fa2c233a-d32b-4c58-b565-d76a717ae93e
Miettinen, Markus S.
15fa5dfd-ae05-4697-9f0d-f38dcf5d6680
Määttä, Jukka
6c2df01d-db83-4d2c-b17e-882094fcdb51
Nencini, Ricky
749bd8ba-7414-499c-9d20-ad9a51db34dc
Ollila, O. H.Samuli
fb8877e8-83cc-4450-821a-951e567a61e3
Piggot, Thomas J.
75829b71-d73b-43d1-b24f-3e70c2c4d0c8
Antila, Hanne
0d3b66cc-5267-48e9-99c3-b4fd3d33979c
Buslaev, Pavel
6c4fef87-961e-4a1a-8af9-011834808c37
Favela-Rosales, Fernando
e94ff5ca-f524-4613-92d6-fa4e895df6d9
Ferreira, Tiago M.
6cb97ad9-84f2-43f0-ab04-f18f2403d69c
Gushchin, Ivan
b14ee732-a1a4-46c7-8cb5-1850b65653f0
Javanainen, Matti
56eca9a4-6434-43b0-8e1c-ef294ff46404
Kav, Batuhan
1cc1a69d-d447-4ece-bc5b-264943e97053
Madsen, Jesper J.
b1ec873c-57bb-4b10-9d8d-2a6ed2ce99da
Melcr, Josef
fa2c233a-d32b-4c58-b565-d76a717ae93e
Miettinen, Markus S.
15fa5dfd-ae05-4697-9f0d-f38dcf5d6680
Määttä, Jukka
6c2df01d-db83-4d2c-b17e-882094fcdb51
Nencini, Ricky
749bd8ba-7414-499c-9d20-ad9a51db34dc
Ollila, O. H.Samuli
fb8877e8-83cc-4450-821a-951e567a61e3
Piggot, Thomas J.
75829b71-d73b-43d1-b24f-3e70c2c4d0c8

Antila, Hanne, Buslaev, Pavel, Favela-Rosales, Fernando, Ferreira, Tiago M., Gushchin, Ivan, Javanainen, Matti, Kav, Batuhan, Madsen, Jesper J., Melcr, Josef, Miettinen, Markus S., Määttä, Jukka, Nencini, Ricky, Ollila, O. H.Samuli and Piggot, Thomas J. (2019) Headgroup structure and cation binding in phosphatidylserine lipid bilayers. Journal of Physical Chemistry B, 123 (43), 9066-9079. (doi:10.1021/acs.jpcb.9b06091).

Record type: Article

Abstract

Phosphatidylserine (PS) is a negatively charged lipid type commonly found in eukaryotic membranes, where it interacts with proteins via nonspecific electrostatic interactions as well as via specific binding. Moreover, in the presence of calcium ions, PS lipids can induce membrane fusion and phase separation. Molecular details of these phenomena remain poorly understood, partly because accurate models to interpret the experimental data have not been available. Here we gather a set of previously published experimental NMR data of C-H bond order parameter magnitudes, |SCH|, for pure PS and mixed PS:PC (phosphatidylcholine) lipid bilayers and augment this data set by measuring the signs of SCH in the PS headgroup using S-DROSS solid-state NMR spectroscopy. The augmented data set is then used to assess the accuracy of the PS headgroup structures in, and the cation binding to, PS-containing membranes in the most commonly used classical molecular dynamics (MD) force fields including CHARMM36, Lipid17, MacRog, Slipids, GROMOS-CKP, Berger, and variants. We show large discrepancies between different force fields and that none of them reproduces the NMR data within experimental accuracy. However, the best MD models can detect the most essential differences between PC and PS headgroup structures. The cation binding affinity is not captured correctly by any of the PS force fields - an observation that is in line with our previous results for PC lipids. Moreover, the simulated response of the PS headgroup to bound ions can differ from experiments even qualitatively. The collected experimental data set and simulation results will pave the way for development of lipid force fields that correctly describe the biologically relevant negatively charged membranes and their interactions with ions. This work is part of the NMRlipids open collaboration project (nmrlipids.blogspot.fi).

Text
manuscriptPS - Accepted Manuscript
Download (6MB)
Text
manuscriptPSsuppl
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 1 October 2019
e-pub ahead of print date: 1 October 2019
Published date: 31 October 2019

Identifiers

Local EPrints ID: 436075
URI: http://eprints.soton.ac.uk/id/eprint/436075
ISSN: 1520-6106
PURE UUID: 96daaa6b-04f3-4022-ad2e-412d4eea1890

Catalogue record

Date deposited: 27 Nov 2019 17:30
Last modified: 07 Oct 2020 06:37

Export record

Altmetrics

Contributors

Author: Hanne Antila
Author: Pavel Buslaev
Author: Fernando Favela-Rosales
Author: Tiago M. Ferreira
Author: Ivan Gushchin
Author: Matti Javanainen
Author: Batuhan Kav
Author: Jesper J. Madsen
Author: Josef Melcr
Author: Markus S. Miettinen
Author: Jukka Määttä
Author: Ricky Nencini
Author: O. H.Samuli Ollila
Author: Thomas J. Piggot

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×