TY - JOUR
T1 - Molecular dynamics simulations of stratum corneum lipid mixtures
T2 - A multiscale perspective
AU - Moore, Timothy C.
AU - Iacovella, Christopher R.
AU - Leonhard, Anne C.
AU - Bunge, Annette L.
AU - McCabe, C.
N1 - Funding Information:
Funding: This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases [grant number R01 AR057886-01 ]; the National Science Foundation [grant number CBET-1028374 ]; the National Energy Research Scientific Computing Center , supported by the Office of Science of the Department of Energy [contract number DE-AC02-05CH11231] ; and the Advanced Computing Center for Research and Education at Vanderbilt University . AL acknowledges support from the National Science Foundation through grant number DMR-1560414 .
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/3/29
Y1 - 2018/3/29
N2 - The lipid matrix of the stratum corneum (SC) layer of skin is essential for human survival; it acts as a barrier to prevent rapid dehydration while keeping potentially hazardous material outside the body. While the composition of the SC lipid matrix is known, the molecular-level details of its organization are difficult to infer experimentally, hindering the discovery of structure-property relationships. To this end, molecular dynamics simulations, which give molecular-level resolution, have begun to play an increasingly important role in understanding these relationships. However, most simulation studies of SC lipids have focused on preassembled bilayer configurations, which, owing to the slow dynamics of the lipids, may influence the final structure and hence the calculated properties. Self-assembled structures would avoid this dependence on the initial configuration, however, the size and length scales involved make self-assembly impractical to study with atomistic models. Here, we report on the development of coarse-grained models of SC lipids designed to study self-assembly. Building on previous work, we present the interactions between the headgroups of ceramide and free fatty acid developed using the multistate iterative Boltzmann inversion method. Validation of the new interactions is performed with simulations of preassembled bilayers and good agreement between the atomistic and coarse-grained models is found for structural properties. The self-assembly of mixtures of ceramide and free fatty acid is investigated and both bilayer and multilayer structures are found to form. This work therefore represents a necessary step in studying SC lipid systems on multiple time and length scales.
AB - The lipid matrix of the stratum corneum (SC) layer of skin is essential for human survival; it acts as a barrier to prevent rapid dehydration while keeping potentially hazardous material outside the body. While the composition of the SC lipid matrix is known, the molecular-level details of its organization are difficult to infer experimentally, hindering the discovery of structure-property relationships. To this end, molecular dynamics simulations, which give molecular-level resolution, have begun to play an increasingly important role in understanding these relationships. However, most simulation studies of SC lipids have focused on preassembled bilayer configurations, which, owing to the slow dynamics of the lipids, may influence the final structure and hence the calculated properties. Self-assembled structures would avoid this dependence on the initial configuration, however, the size and length scales involved make self-assembly impractical to study with atomistic models. Here, we report on the development of coarse-grained models of SC lipids designed to study self-assembly. Building on previous work, we present the interactions between the headgroups of ceramide and free fatty acid developed using the multistate iterative Boltzmann inversion method. Validation of the new interactions is performed with simulations of preassembled bilayers and good agreement between the atomistic and coarse-grained models is found for structural properties. The self-assembly of mixtures of ceramide and free fatty acid is investigated and both bilayer and multilayer structures are found to form. This work therefore represents a necessary step in studying SC lipid systems on multiple time and length scales.
KW - Ceramide
KW - Coarse-grained
KW - Multistate iterative Boltzmann inversion
KW - Self-assembly
KW - Skin
UR - http://www.scopus.com/inward/record.url?scp=85029499182&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2017.09.040
DO - 10.1016/j.bbrc.2017.09.040
M3 - Article
C2 - 28911866
AN - SCOPUS:85029499182
SN - 0006-291X
VL - 498
SP - 313
EP - 318
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -