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Title: Behavior of Bilayer Leaflets in Asymmetric Model Membranes: Atomistic Simulation Studies

Journal Article · · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry
 [1];  [2];  [3];  [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Molecular Biophysics
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Joint Inst. for Neutron Sciences. Biology and Soft Matter Division
  3. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Joint Inst. for Neutron Sciences. Biology and Soft Matter Division; Univ. of Tennessee, Knoxville, TN (United States). Bredesen Center for Interdisciplinary Research and Graduate Education

Spatial organization within lipid bilayers is an important feature for a range of biological processes. Leaflet compositional asymmetry and lateral lipid organization are just two of the ways in which membrane structure appears to be more complex than initially postulated by the fluid mosaic model. This raises the question of how the phase behavior in one bilayer leaflet may affect the apposing leaflet and how one begins to construct asymmetric model systems to investigate these interleaflet interactions. In this paper, we report on all-atom molecular dynamics simulations (a total of 4.1 μs) of symmetric and asymmetric bilayer systems composed of liquid-ordered (Lo) or liquid-disordered (Ld) leaflets, based on the nanodomain-forming POPC/DSPC/cholesterol system. We begin by analyzing an asymmetric bilayer with leaflets derived from simulations of symmetric Lo and Ld bilayers. In this system, we observe that the properties of the Lo and Ld leaflets are similar to those of the Lo and Ld leaflets in corresponding symmetric systems. However, it is not obvious that mixing the equilibrium structures of their symmetric counterparts is the most appropriate way to construct asymmetric bilayers nor that these structures will manifest interleaflet couplings that lead to domain registry/antiregistry. We therefore constructed and simulated four additional asymmetric bilayer systems by systematically adding or removing lipids in the Ld leaflet to mimic potential density fluctuations. We find that the number of lipids in the Ld leaflet affects its own properties, as well as those of the apposing Lo leaflet. Collectively, the simulations reveal the presence of weak acyl chain interdigitation across bilayer leaflets, suggesting that interdigitation alone does not contribute significantly to the interleaflet coupling in nonphase-separated bilayers of this chemical composition. Finally, however, the properties of both leaflets appear to be sensitive to changes in in-plane lipid packing, possibly providing a mechanism for interleaflet coupling by modulating local density and/or curvature fluctuations.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1327657
Journal Information:
Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry, Vol. 120, Issue 33; ISSN 1520-6106
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 14 works
Citation information provided by
Web of Science

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Cited By (1)

Chain ordering of phospholipids in membranes containing cholesterol: what matters? journal January 2021

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