Line tension of the pore edge in phospholipid/cholesterol bilayer from stretch molecular dynamics simulation

Abstract

The line tension of the pore in a phospholipid bilayer is important for pore-mediated molecular transport techniques. To understand the cholesterol effects on the line tension of the pore edge at the molecular level, we perform molecular dynamics simulations of phospholipid bilayers with a pore containing cholesterol in different concentrations (0, 20, and 40 mol%). The bilayer with a pore is prepared by using an equibiaxial stretching simulation. The stretched bilayer with a pore is subsequently compressed and the pore spontaneously closes when the applied areal strain of the bilayer is below a certain value. Using the pore closure areal strain and a free energy model of a stretched bilayer with a pore, the upper and lower limits of the line tensions for the bilayers containing cholesterol at 0, 20, and 40 mol% are estimated to be 17.0-48.2, 54.5-100, and 170-261 pN, respectively. The increasing tendency of the line tension qualitatively agrees with that observed experimentally. The pores in the cholesterol-containing bilayers are lined with several cholesterol molecules, which might increase the bending rigidity of the pore edge, and result in the higher line tension of the cholesterol-containing bilayer. The considerable dependency of the line tension on the bilayer compositions might be useful to explain the large variations of the transduction efficiency observed with sonoporation treatment.

Development of a charged model of the SARS-CoV-2 viral surface

“…The results of this computational model are now used to estimate the effectiveness of RF fields to disinfect/inactivate a viral particle by rupturing its membrane. The formation of pores in the membrane at strains 50% is consistent with other MD studies of flat lipid bilayers containing cholesterol [33] . The formation of the pores would be associated with rupture thresholds in the membrane; and thus, the computational model suggests that a strain threshold of 50% would be associated with membrane rupture.…”

A rapid and highly sensitive biomarker detection platform based on a temperature-responsive liposome-linked immunosorbent assay

“…When liposomes that contain SQR22 in the lipid bilayer membrane were exposed to temperatures lower than the critical temperature, the line tension of the pure DPPC regions was reported to be approximately 10-13 pN 25,26 . This line tension contributes to exclude the molecules loaded in the lipid bilayer, such as SQR22, from the DPPC region, which in turn increases the line tension 27 , resulting in the packing of the SQR22 molecules together and aggregation-caused quenching. When the liposomes are heated close to the phase transition temperature, the line tension drastically decreases and then vanishes according to the following law: λ(T) is proportional to (1 − T/T c ), where T c is the phase transition temperature of the liposomes and T ≤ T c 22 .…”

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“…The number of MD simulation studies of tension-induced pore formation in lipid bilayers has increased over the past 15 years (e.g., Tolpekina et al 2004;Wohlert et al 2006;Shigematsu et al 2015Shigematsu et al , 2016Awasthi and Hub 2016;Akimov et al 2017a). Special sampling techniques such as the umbrella sampling method have been used to obtain the free energy profile for tension-induced pore formation using MD simulations, but the results obtained greatly depend on the reaction coordinates selected.…”