TY - JOUR
T1 - Effects of cholesterol on water permittivity of biomimetic ion pair amphiphile bilayers
T2 - Interplay between membrane bending and molecular packing
AU - Tien, Wu Jhao
AU - Chen, Kun You
AU - Huang, Fong Yin
AU - Chiu, Chi Cheng
N1 - Funding Information:
Funding: This work was partially supported by the Hierarchical Green-Energy Materials (Hi-GEM) Research Center, from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Projec tby the Ministry of Education (MOE) in Taiwan. The authors also acknowledge the financial supports by the Ministry of Science and Technology of Taiwan through Grant Nos. MOST 106-2221-E-006-199 and MOST 107-2221-E-006-102. The computational resource was partially supported by the high-performance cluster computing (HPCC) service from computer and network center of National Cheng Kung University.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic amphiphiles, is an inexpensive phospholipid substitute to fabricate vesicles with various pharmaceutical applications. Modulating the physicochemical and permeation properties of IPA vesicles are important for carrier designs. Here, we applied molecular dynamics simulations to examine the cholesterol effects on the structures, mechanics, and water permittivity of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium-hexadecylsulfate (DTMA-HS) IPA bilayers. Structural and mechanical analyses indicate that both IPA systems are in gel phase at 298 K. Adding cholesterol induces alkyl chain ordering around the rigid sterol ring and increases the cavity density within the hydrophilic region of both IPA bilayers. Furthermore, the enhanced alkyl chain ordering and the membrane deformation energy induced by cholesterol increase the permeation free energy penalty. In contrast, cholesterol has minor effects on the water local diffusivities within IPA membranes. Overall, the cholesterol reduces the water permittivity of rigid IPA membranes due to the synergistic effects of increased alkyl chain ordering and enhanced membrane mechanical modulus. The results provide molecular insights into the effects of molecular packing and mechanical deformations on the water permittivity of biomimetic IPA membranes, which is critical for designing IPA vesicular carriers.
AB - Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic amphiphiles, is an inexpensive phospholipid substitute to fabricate vesicles with various pharmaceutical applications. Modulating the physicochemical and permeation properties of IPA vesicles are important for carrier designs. Here, we applied molecular dynamics simulations to examine the cholesterol effects on the structures, mechanics, and water permittivity of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium-hexadecylsulfate (DTMA-HS) IPA bilayers. Structural and mechanical analyses indicate that both IPA systems are in gel phase at 298 K. Adding cholesterol induces alkyl chain ordering around the rigid sterol ring and increases the cavity density within the hydrophilic region of both IPA bilayers. Furthermore, the enhanced alkyl chain ordering and the membrane deformation energy induced by cholesterol increase the permeation free energy penalty. In contrast, cholesterol has minor effects on the water local diffusivities within IPA membranes. Overall, the cholesterol reduces the water permittivity of rigid IPA membranes due to the synergistic effects of increased alkyl chain ordering and enhanced membrane mechanical modulus. The results provide molecular insights into the effects of molecular packing and mechanical deformations on the water permittivity of biomimetic IPA membranes, which is critical for designing IPA vesicular carriers.
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U2 - 10.3390/ijms20133252
DO - 10.3390/ijms20133252
M3 - Article
C2 - 31269714
AN - SCOPUS:85068694218
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 13
M1 - 3252
ER -