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Effects of lipid heterogeneity on model human brain lipid membranes

Effects of lipid heterogeneity on model human brain lipid membranes
Effects of lipid heterogeneity on model human brain lipid membranes

Cell membranes naturally contain a heterogeneous lipid distribution. However, homogeneous bilayers are commonly preferred and utilised in computer simulations due to their relative simplicity, and the availability of lipid force field parameters. Recently, experimental lipidomics data for the human brain cell membranes under healthy and Alzheimer's disease (AD) conditions were investigated, since disruption to the lipid composition has been implicated in neurodegenerative disorders, including AD [R. B. Chan et al., J. Biol. Chem., 2012, 287, 2678-2688]. In order to observe the effects of lipid complexity on the various bilayer properties, molecular dynamics simulations were used to study four membranes with increasing heterogeneity: a pure POPC membrane, a POPC and cholesterol membrane in a 1 : 1 ratio (POPC-CHOL), and to our knowledge, the first realistic models of a healthy brain membrane and an Alzheimer's diseased brain membrane. Numerous structural, interfacial, and dynamical properties, including the area per lipid, interdigitation, dipole potential, and lateral diffusion of the two simple models, POPC and POPC-CHOL, were analysed and compared to those of the complex brain models consisting of 27 lipid components. As the membranes gain heterogeneity, a number of alterations were found in the structural and dynamical properties, and more significant differences were observed in the lateral diffusion. Additionally, we observed snorkeling behaviour of the lipid tails that may play a role in the permeation of small molecules across biological membranes. In this work, atomistic description of realistic brain membrane models is provided, which can add insight towards the permeability and transport pathways of small molecules across these membrane barriers.

1744-683X
126-135
Yee, Sze May
1252799b-e2df-46b3-8364-8dfd6a4932ec
McLain, Sylvia E.
f0b6c048-e499-4eca-801e-359ac928f502
Lorenz, Christian D.
080b1193-25c1-49da-968a-ef522fdbec59
Gillams, Richard
89341fe4-db94-4d27-a5be-c092e2e8de5b
Yee, Sze May
1252799b-e2df-46b3-8364-8dfd6a4932ec
McLain, Sylvia E.
f0b6c048-e499-4eca-801e-359ac928f502
Lorenz, Christian D.
080b1193-25c1-49da-968a-ef522fdbec59
Gillams, Richard
89341fe4-db94-4d27-a5be-c092e2e8de5b

Yee, Sze May, McLain, Sylvia E., Lorenz, Christian D. and Gillams, Richard (2021) Effects of lipid heterogeneity on model human brain lipid membranes. Soft Matter, 17 (1), 126-135. (doi:10.1039/D0SM01766C).

Record type: Article

Abstract

Cell membranes naturally contain a heterogeneous lipid distribution. However, homogeneous bilayers are commonly preferred and utilised in computer simulations due to their relative simplicity, and the availability of lipid force field parameters. Recently, experimental lipidomics data for the human brain cell membranes under healthy and Alzheimer's disease (AD) conditions were investigated, since disruption to the lipid composition has been implicated in neurodegenerative disorders, including AD [R. B. Chan et al., J. Biol. Chem., 2012, 287, 2678-2688]. In order to observe the effects of lipid complexity on the various bilayer properties, molecular dynamics simulations were used to study four membranes with increasing heterogeneity: a pure POPC membrane, a POPC and cholesterol membrane in a 1 : 1 ratio (POPC-CHOL), and to our knowledge, the first realistic models of a healthy brain membrane and an Alzheimer's diseased brain membrane. Numerous structural, interfacial, and dynamical properties, including the area per lipid, interdigitation, dipole potential, and lateral diffusion of the two simple models, POPC and POPC-CHOL, were analysed and compared to those of the complex brain models consisting of 27 lipid components. As the membranes gain heterogeneity, a number of alterations were found in the structural and dynamical properties, and more significant differences were observed in the lateral diffusion. Additionally, we observed snorkeling behaviour of the lipid tails that may play a role in the permeation of small molecules across biological membranes. In this work, atomistic description of realistic brain membrane models is provided, which can add insight towards the permeability and transport pathways of small molecules across these membrane barriers.

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Published date: 2021

Identifiers

Local EPrints ID: 448241
URI: http://eprints.soton.ac.uk/id/eprint/448241
ISSN: 1744-683X
PURE UUID: 6fee6dd7-31af-4891-842c-75259bf2db25
ORCID for Richard Gillams: ORCID iD orcid.org/0000-0002-8597-8723

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Date deposited: 15 Apr 2021 16:35
Last modified: 05 Jun 2024 17:47

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Contributors

Author: Sze May Yee
Author: Sylvia E. McLain
Author: Christian D. Lorenz
Author: Richard Gillams ORCID iD

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