Modelling and simulations of phosphatidylcholine bilayers containing diacylglycerol (DAG): clues to the importance of changing membrane properties for the invertebrate phototransduction
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1
Department of Physics, University of Oulu, Finland
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2
University of Oulu, Department of Biochemistry, Finland
DAGs are lipid molecules capable of triggering a wide range of biological responses. They serve as second messengers by regulating both the translocation to the membrane compartment and the activation of C1 domain-bearing proteins. They are also involved in other phenomena of great biophysical importance, like the facilitation of membrane fusion and the activation of certain TRP channels, which are involved -among other processes- in invertebrate phototransduction. Experimental studies have led to the sug- gestion that cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C (PLC), yielding membrane soluble DAG, could be a crucial step to produce mechani- cal stress contributing the channel gating [1]. However, the activation mechanism re- mains unknown. Our present studies are motivated by the need to obtain a deeper in- sight in the physical mechanisms underlying phototransduction, as well as other DAG- mediated processes, malfunctions of which are associated with a large number of dis- ease states.
In order to investigate the physical properties of DAG-containing membranes in the atomic scale, we developed an atomic level GROMOS force field-based model of bio- logically relevant DAG isoforms and incorporated them into model phosphatidylcholine bilayer systems developed earlier [2]. We subsequently employed extensive molecular dynamics simulations of the mixed hydrated bilayer systems. Our studies allow us to observe overall thermodynamic and structural effects as a function of increasing DAG concentration and varying chain composition. The effects are well in accordance with the experimental observations, whenever comparison is possible, which enhances the fidelity of our model. Moreover, we obtain information related to the mobility of DAG and its local effects that are not readily accessible by experimental means.
Our study highlights the importance of the modulation of several physical properties of lipid bilayers by DAG in a local level, which could affect the biological responses of DAG. It also provides a valid model for future studies on the interactions of lipid bi- layers with DAG-responsive proteins by computational means. Presently, the DAG model is modified to enable the studies of the effects of PIP2 and free fatty acids.
References
[1] R. H. Hardie and K. Franze, Photomechanical Responses in Drosophila Photoreceptors, Science, 338 (2012) 260.
[2] D. Poger and A. E. Mark, On the Validation of Molecular Dynamics Simulations of Saturated and cis-Monounsaturated Phosphatidylcholine Lipid Bilayers: A Comparison with Experiment, J. Chem. Theory Comput. 6 (2010) 325.
Keywords:
diacylglycerol,
MD simulations,
POPC membrane,
TRP channels,
lipid signaling
Conference:
International Conference on Invertebrate Vision, Fjälkinge, Sweden, 1 Aug - 8 Aug, 2013.
Presentation Type:
Poster presentation preferred
Topic:
Transduction, signalling and coding
Citation:
Beis
I,
Juffer
A,
Weckstrom
M and
Hyvönen
MT
(2019). Modelling and simulations of phosphatidylcholine bilayers containing diacylglycerol (DAG): clues to the importance of changing membrane properties for the invertebrate phototransduction.
Front. Physiol.
Conference Abstract:
International Conference on Invertebrate Vision.
doi: 10.3389/conf.fphys.2013.25.00080
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Received:
27 Feb 2013;
Published Online:
09 Dec 2019.
*
Correspondence:
Mr. Ioannis Beis, Department of Physics, University of Oulu, Oulu, University of Oulu, 90014, Finland, Ioannis.Beis@oulu.fi