Studies of cholesterol structures in phospholipid bilayers

Carl S. Helrich; Carl S. Helrich

doi:10.3934/biophy.2017.3.415

AIMS Biophysics

2017, Volume 4, Issue 3: 415-437. doi: 10.3934/biophy.2017.3.415

Previous Article Next Article

Research article Special Issues

Studies of cholesterol structures in phospholipid bilayers

Carl S. Helrich ^,

Department of Physics, Goshen College, Goshen, Indiana, USA

Received: 04 April 2017 Accepted: 26 May 2017 Published: 23 June 2017

Experiments and Monte Carlo (MC) simulations on ergosterol/nystatin channels providestrong evidence for superlattices in ergosterol/phospholipid planar bilayers. Monte Carlo simulationsalso revealed the presence of ergosterol superlattice domains in artificial vesicle membranes. MC simulation for ergosterol densities in these domains matched the dehydroergosterol (DHE) fluorescence measurements by Chong of dehydroergosterol density in multilamellar vesicles. Withergosterol/nystatin channels on the boundaries of these domains MC simulations produced agreement with experimental measurements of ergosterol/nystatin channel currents. These techniques, however, failed for cholesterol/nystatin channels. Although studies of initial dynamics in the formation ofergosterol/nystatin channels confirm ergosterol superlattices, they fail for cholesterol/nystatin channels. However a Fast Fourier Transform based study of the frequency of fluctuation spikes present inlow density cholesterol/nystatin channel currents revealed a dependence of spike frequency oncholesterol mol fraction which matched cholesterol density from DHE/cholesterol/DMPC fluorescence experiments. This indicates the probable presence of superlattices in cholesterol structures in phospholipid bilayers. The causal relationship between these statistical channel fluctuations andcholesterol structure is notable in its own right.
- ergosterol,
- cholesterol,
- nystatin,
- phospholipid,
- bilayer,
- vesicles,
- superlattice
Citation: Carl S. Helrich. Studies of cholesterol structures in phospholipid bilayers[J]. AIMS Biophysics, 2017, 4(3): 415-437. doi: 10.3934/biophy.2017.3.415

Related Papers:

Abstract

Experiments and Monte Carlo (MC) simulations on ergosterol/nystatin channels providestrong evidence for superlattices in ergosterol/phospholipid planar bilayers. Monte Carlo simulationsalso revealed the presence of ergosterol superlattice domains in artificial vesicle membranes. MC simulation for ergosterol densities in these domains matched the dehydroergosterol (DHE) fluorescence measurements by Chong of dehydroergosterol density in multilamellar vesicles. Withergosterol/nystatin channels on the boundaries of these domains MC simulations produced agreement with experimental measurements of ergosterol/nystatin channel currents. These techniques, however, failed for cholesterol/nystatin channels. Although studies of initial dynamics in the formation ofergosterol/nystatin channels confirm ergosterol superlattices, they fail for cholesterol/nystatin channels. However a Fast Fourier Transform based study of the frequency of fluctuation spikes present inlow density cholesterol/nystatin channel currents revealed a dependence of spike frequency oncholesterol mol fraction which matched cholesterol density from DHE/cholesterol/DMPC fluorescence experiments. This indicates the probable presence of superlattices in cholesterol structures in phospholipid bilayers. The causal relationship between these statistical channel fluctuations andcholesterol structure is notable in its own right.

References

[1]	Ali MR, Cheng KH, Huang J (2007) Assess the nature of cholesterollipid interactions through the chemical potential of cholesterol in phosphatidylcholine bilayers. PNAS USA 104: 5372–5377.
[2]	Anderson TG, McConnell HM (2001) Condensed complexes and the calorimetry of cholesterol-phospholipid bilayers. Biophys J 8: 2774–2785.
[3]	Balyimez S, Park S, Huang J (2011) The maximum solubility of cholesterol in POPC/POPE lipid mixtures. Biophys J 100: 625a.
[4]	Chong LG (1994) Evidence for regular distribution of sterols in liquid crystalline phosphatidylcholine bilayers. PNAS USA 91: 10069–10073. doi: 10.1073/pnas.91.21.10069
[5]	Chong LG, Olsher M (2004) Fluorescence studies of the existence and functional importance of regular distributions in liposomal membranes. Soft Mat 2: 85–108. doi: 10.1081/SMTS-200056098
[6]	Coutinho A, Prieto M (2003) Cooperative partition model of nystatin interaction with phospholipid vesicles. Biophys J 84: 3061–3078. doi: 10.1016/S0006-3495(03)70032-0
[7]	Coutinho A, Silva L, Fedorov A, et al. (2004) Cholesterol and ergosterol influence nystatin surface aggregation: relation to pore formation. Biophys J 87: 3264–3276. doi: 10.1529/biophysj.104.044883
[8]	Dai J, Alwarawrah M, Huang J (2010) Study of the cholesterol umbrella effect in DPPC and DOPC bilayers by molecular dynamics simulation. Biophys J 98: 489a.
[9]	Ege C, Ratajczak MK, Majewski J, et al. (2006) Evidence for lipid/cholesterol ordering in model lipid membranes. Biophys J 91: L01–L03. doi: 10.1529/biophysj.106.085134
[10]	Gibbs JW (1902) Elementary Principles in Statistical Mechanics, New Haven: Yale University Press.
[11]	Helrich CS (2009) Modern Thermodynamics with Statistical Mechanics, Berlin: Springer.
[12]	Helrich CS, Schmucker JA, Woodbury DJ (2006) Evidence that nystatin channels form at the boundaries, not the interiors of lipid domains. Biophys J 91: 1116–1127. doi: 10.1529/biophysj.105.076281
[13]	Huang J (2002) Exploration of molecular interactions in cholesterol superlattices: effect of multibody interactions. Biophys J 83: 1014–1025. doi: 10.1016/S0006-3495(02)75227-2
[14]	Huang J, Feigenson GW (1999) A microscopic interaction model of maximum solubility of cholesterol in lipid bilayers. Biophys J 76: 2142–2157. doi: 10.1016/S0006-3495(99)77369-8
[15]	Keller SL, Anderson TG, McConnell HM (2000) Miscibility critical pressures in monolayers of ternary lipid mixtures. Biophys J 79: 2033–2042. doi: 10.1016/S0006-3495(00)76451-4
[16]	Kuzmin PI, Akimov SA, Chimadzhev YA (2005) Line tension and interaction energies of membrane rafts calculated from lipid splay and tilt. Biophys J 88: 1120–1133. doi: 10.1529/biophysj.104.048223
[17]	Liu F, Sugar IP, Chong PL (1997) Cholesterol and ergosterol superlattices in three-component liquid crystalline lipid bilayers as revealed by dehydroergosterol fluorescence. Biophys J 72: 2243–2254. doi: 10.1016/S0006-3495(97)78868-4
[18]	Metropolis N, Rosenbluth AW, Rosenbluth MN, et al. (1953) Equation of state calculations by fast computing machines. J Chem Phys 21: 1087–1092. doi: 10.1063/1.1699114
[19]	Nishimura SY, Vrljic M, Klein LO, et al. (2006) Cholesterol depletion induces solid-like regions in the plasma membrane. Biophys J 90: 927–938. doi: 10.1529/biophysj.105.070524
[20]	Parker A, Miles K, Cheng KH, et al. (2004) Lateral distribution of cholesterol in dioleoylphosphatidylcholine lipid bilayers: cholesterol-phospholipid interactions at high cholesterol limit. Biophys J 86: 1532–1544. doi: 10.1016/S0006-3495(04)74221-6
[21]	Radhakrishnan A, McConnell HM (1999) Condensed complexes of cholesterol and phospholipids. Biophys J 77: 1507–1517. doi: 10.1016/S0006-3495(99)76998-5
[22]	Radhakrishnan A, Anderson TG, McConnell HM (2000) Condensed complexes, rafts, and the chemical activity of cholesterol in membranes. PNAS USA 97: 12422–12427. doi: 10.1073/pnas.220418097
[23]	Richardson G, Cummings LJ, Harris HJ, et al. (2007) Toward a mathematical model of the assembly and disassembly of membrane microdomains: comparison with experimental models. Biophys J 92: 4145–4156. doi: 10.1529/biophysj.106.090233
[24]	Schroeder F, Barenholz Y, Gratton E, et al. (1987) A fluorescence study of dehydroergosterol in phosphatidylcholine bilayer vesicles. Biochemistry 26: 2441–2448. doi: 10.1021/bi00383a007
[25]	Sintes T, Baumgrtner A (1997) Protein attraction in membranes induced by lipid fluctuations. Biophys J 73: 2251–2259. doi: 10.1016/S0006-3495(97)78257-2
[26]	Somerharju PJ, Virtanen JA, Eklund KK, et al. (1985) 1-Palmitoyl-2-pyrenedecanoyl glycerophospholipids as membrane probes: evidence for regular distribution in liquid-crystalline phosphatidylcholine bilayers. Biochemistry 24: 2773–2781. doi: 10.1021/bi00332a027
[27]	Sugar IP, Tang D, Chong PLG (1994) Monte Carlo simulation of lateral distribution of molecules in a two-component lipid membrane. Effect of long-range repulsive interactions. J Phys Chem 98: 7201–7210.
[28]	Tang D, Chong PL (1992) E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations. Biophys J 63: 903–910.
[29]	Venegas B, Sugr IP, Chong PLG (2007) Critical factors for detection of biphasic changes in membrane properties at specific sterol mole fractions for maximal superlattice formation. J Phys Chem B 111: 5180–5192. doi: 10.1021/jp070222k
[30]	Virtanen JA, Somerharju P, Kinnunen PKJ (1988) Prediction of patterns for the regular distribution of soluted guest molecules in liquid crystalline phospholipid membranes. J Mol Electron 4: 233–236.
[31]	Vrljic M, Nishimura SY, Moerner WE, et al. (2005) Cholesterol depletion suppresses the translational diffusion of class II major histocompatibility complex proteins in the plasma membrane. Biophys J 88: 334–347. doi: 10.1529/biophysj.104.045989

Reader Comments

Your name:*

Email:*
© 2017 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)