(561h) Multiscale Modeling of the Structure and Permeability of Self-Assembled Stratum Corneum Lipid Membranes
AIChE Annual Meeting
2022
2022 Annual Meeting
Materials Engineering and Sciences Division
Polymer Simulations: Methods and Applications
Wednesday, November 16, 2022 - 5:30pm to 5:45pm
To examine the structure and properties of SC lipid mixtures, we employ a multiscale modeling approach that enables efficient atomistic examination of self-assembled multi-layer SC lipid membranes [4]. Here, atomistic simulations are used to parameterize CG models via the multi-state iterative Boltzmann inversion (MS-IBI) method [3]. In the MS-IBI method, optimizations are performed simultaneously over a range of target thermodynamic and structural statepoints, as well as using different ensembles to ensure appropriate relationships are captured (e.g., density-pressure relationships), resulting in CG force fields with a high degree of transferability between different lipids and states. The MS-IBI derived CG force fields are used to perform self-assembly of membranes composed of the SC lipids [2,4,5], including large multi-layer systems. The self-assembled structures from the CG simulation are then used to construct more realistic pre-assembled atomistic configurations. In this approach, the self-assembled lamellae define the initial atomistic morphology (e.g., in-plane arrangement of lipid components) and ceramide conformations (e.g., hairpin or extended configurations of each molecule) in each layer. Atomistic simulations of these initial configurations then uses standard relaxation procedures to obtain atomistically detailed configurations that should be more representative of experiment. Here, we utilize this multiscale approach to provide detailed examination of the self-assembly, lipid morphology, lipid-tail ordering, hydrogen bonding, free energy profiles, and diffusion coefficients for different lipid mixtures, in order to establish relationships between composition and permeability of multi-layer SC lipid membranes.
[1] Moore T.C., Hartkamp R., Iacovella C.R., Bunge A.L., McCabe C. The Influence of Ceramide Tail Length on the Structure of Bilayers Composed of Stratum Corneum Lipids, Biophysical Journal, 2018 114, 113-125
[2] Moore T. C., Iacovella, C. R., Hartkamp, R., Bunge, A. L. & McCabe, C. A Coarse-Grained Model of Stratum Corneum Lipids: Free Fatty Acids and Ceramide NS. J. Phys. Chem. B 2016 120, 9944â9958
[3] Moore T. C., Iacovella, C. R. & McCabe, C. Derivation of coarse-grained potentials via multistate iterative Boltzmann inversion. J. Chem. Phys. 2014, 140, 224104
[4] Shamaprasad P, Moore T.C. Xia, D., Iacovella C.R., Bunge A.L., McCabe C., Multiscale simulation of ternary stratum corneum lipid mixtures: Effects of cholesterol composition, under-review
[5] Moore T.C., Iacovella C.R., Leonhard A., Bunge A.L., McCabe C., Molecular Dynamics Simulations of Stratum Corneum Lipid Mixtures: A Multiscale Perspective, Biochemical and Biophysical Research Communications, 2018 498, 313-318