Interaction of the mononucleotide UMP with a fluid phospholipid bilayer

Sreeja Sasidharan, Simon Pochinda, Paninnguaq Naja Elgaard-Jørgensen, Sudha Rajamani, Himanshu Khandelia*, V. A. Raghunathan

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Interaction between mononucleotides and lipid membranes is believed to have played an important role in the origin of life on Earth. Studies on mononucleotide-lipid systems hitherto have focused on the influence of the lipid environment on the organization of the mononucleotide molecules, and the effect of the latter on the confining medium has not been investigated in detail. We have probed the interaction of the mononucleotide, uridine 5′-monophosphate (UMP), and its disodium salt (UMPDSS) with fluid dimyristoylphosphatidylcholine (DMPC) membranes, using small-angle X-ray scattering (SAXS), cryogenic scanning electron microscopy (cryo-SEM) and computer simulations. UMP adsorbs and charges the lipid membrane, resulting in the formation of unilamellar vesicles in dilute solutions. Adsorption of UMP reduces the bilayer thickness of DMPC. UMPDSS has a much weaker effect on interbilayer interactions. These observations are in very good agreement with the results of an all-atom molecular dynamics simulation of these systems. In the presence of counterions, such as Na+, UMP forms small aggregates in water, which bind to the bilayer without significantly perturbing it. The phosphate moiety in the lipid headgroup is found to bind to the hydrogens from the sugar ring of UMP, while the choline group tends to bind to the two oxygens from the nucleotide base. These studies provide important insights into lipid-nucleotide interactions and the effect of the nucleotide on lipid membranes.

OriginalsprogEngelsk
TidsskriftSoft Matter
Vol/bind15
Udgave nummer40
Sider (fra-til)8129-8136
Antal sider8
ISSN1744-683X
DOI
StatusUdgivet - 1. jan. 2019

Fingeraftryk

Uridine Monophosphate
lipids
Phospholipids
Fluids
fluids
Membrane Lipids
nucleotides
Dimyristoylphosphatidylcholine
Lipids
Nucleotides
membranes
interactions
Salts
Unilamellar Liposomes
salts
Computer simulation
choline
Choline
X ray scattering
Sugars

Citer dette

Sasidharan, S., Pochinda, S., Elgaard-Jørgensen, P. N., Rajamani, S., Khandelia, H., & Raghunathan, V. A. (2019). Interaction of the mononucleotide UMP with a fluid phospholipid bilayer. Soft Matter, 15(40), 8129-8136. https://doi.org/10.1039/c9sm01257e
Sasidharan, Sreeja ; Pochinda, Simon ; Elgaard-Jørgensen, Paninnguaq Naja ; Rajamani, Sudha ; Khandelia, Himanshu ; Raghunathan, V. A. / Interaction of the mononucleotide UMP with a fluid phospholipid bilayer. I: Soft Matter. 2019 ; Bind 15, Nr. 40. s. 8129-8136.
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Sasidharan, S, Pochinda, S, Elgaard-Jørgensen, PN, Rajamani, S, Khandelia, H & Raghunathan, VA 2019, 'Interaction of the mononucleotide UMP with a fluid phospholipid bilayer', Soft Matter, bind 15, nr. 40, s. 8129-8136. https://doi.org/10.1039/c9sm01257e

Interaction of the mononucleotide UMP with a fluid phospholipid bilayer. / Sasidharan, Sreeja; Pochinda, Simon; Elgaard-Jørgensen, Paninnguaq Naja; Rajamani, Sudha; Khandelia, Himanshu; Raghunathan, V. A.

I: Soft Matter, Bind 15, Nr. 40, 01.01.2019, s. 8129-8136.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Interaction of the mononucleotide UMP with a fluid phospholipid bilayer

AU - Sasidharan, Sreeja

AU - Pochinda, Simon

AU - Elgaard-Jørgensen, Paninnguaq Naja

AU - Rajamani, Sudha

AU - Khandelia, Himanshu

AU - Raghunathan, V. A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Interaction between mononucleotides and lipid membranes is believed to have played an important role in the origin of life on Earth. Studies on mononucleotide-lipid systems hitherto have focused on the influence of the lipid environment on the organization of the mononucleotide molecules, and the effect of the latter on the confining medium has not been investigated in detail. We have probed the interaction of the mononucleotide, uridine 5′-monophosphate (UMP), and its disodium salt (UMPDSS) with fluid dimyristoylphosphatidylcholine (DMPC) membranes, using small-angle X-ray scattering (SAXS), cryogenic scanning electron microscopy (cryo-SEM) and computer simulations. UMP adsorbs and charges the lipid membrane, resulting in the formation of unilamellar vesicles in dilute solutions. Adsorption of UMP reduces the bilayer thickness of DMPC. UMPDSS has a much weaker effect on interbilayer interactions. These observations are in very good agreement with the results of an all-atom molecular dynamics simulation of these systems. In the presence of counterions, such as Na+, UMP forms small aggregates in water, which bind to the bilayer without significantly perturbing it. The phosphate moiety in the lipid headgroup is found to bind to the hydrogens from the sugar ring of UMP, while the choline group tends to bind to the two oxygens from the nucleotide base. These studies provide important insights into lipid-nucleotide interactions and the effect of the nucleotide on lipid membranes.

AB - Interaction between mononucleotides and lipid membranes is believed to have played an important role in the origin of life on Earth. Studies on mononucleotide-lipid systems hitherto have focused on the influence of the lipid environment on the organization of the mononucleotide molecules, and the effect of the latter on the confining medium has not been investigated in detail. We have probed the interaction of the mononucleotide, uridine 5′-monophosphate (UMP), and its disodium salt (UMPDSS) with fluid dimyristoylphosphatidylcholine (DMPC) membranes, using small-angle X-ray scattering (SAXS), cryogenic scanning electron microscopy (cryo-SEM) and computer simulations. UMP adsorbs and charges the lipid membrane, resulting in the formation of unilamellar vesicles in dilute solutions. Adsorption of UMP reduces the bilayer thickness of DMPC. UMPDSS has a much weaker effect on interbilayer interactions. These observations are in very good agreement with the results of an all-atom molecular dynamics simulation of these systems. In the presence of counterions, such as Na+, UMP forms small aggregates in water, which bind to the bilayer without significantly perturbing it. The phosphate moiety in the lipid headgroup is found to bind to the hydrogens from the sugar ring of UMP, while the choline group tends to bind to the two oxygens from the nucleotide base. These studies provide important insights into lipid-nucleotide interactions and the effect of the nucleotide on lipid membranes.

U2 - 10.1039/c9sm01257e

DO - 10.1039/c9sm01257e

M3 - Journal article

VL - 15

SP - 8129

EP - 8136

JO - Soft Matter

JF - Soft Matter

SN - 1744-683X

IS - 40

ER -

Sasidharan S, Pochinda S, Elgaard-Jørgensen PN, Rajamani S, Khandelia H, Raghunathan VA. Interaction of the mononucleotide UMP with a fluid phospholipid bilayer. Soft Matter. 2019 jan 1;15(40):8129-8136. https://doi.org/10.1039/c9sm01257e