INTRODUCTIONThe cell membrane is primarily composed of a diverse phospholipid (lipid) bilayer with many phospholipid types, each of which is comprised of a hydrophilic headgroup (pointing outward in contact with aqueous environment) and two hydrophobic hydrocarbon chains (pointing inward with the two monolayers facing each other). Lipid type affects the molecular structures of the headgroup and tail groups, which can influence nanomechanics of the membrane under mechanical loading and affect cell viability. Hence, using molecular dynamics (MD) simulations, the current study investigated seven common membrane phospholipids and examined the impact of their structural differences on membrane failure and mechanoporation damage during tensile deformation.METHODSSeven bilayer membranes, each composed of different phospholipids, generally notated as “[n:a/m:b]headgroup” (in which n, m and a, b are respectively the number of carbon segments and double bonds in the two hydrocarbon tails and headgroup indicates the type of headgroup, which includes phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in this study), are simulated using GROMACS and CHARMM36 all-atom force field. The phospholipids include [16:0/18:2]PC, [16:1/18:1]PC, [16:0/18:1]PC, [16:0/18:0]PC, [18:0/18:1]PC, [16:0/16:1]PC, and [16:0/18:1]PE. They are abundant in the cell membrane and differ from each other in their headgroup, chain length, or saturation (number of double bonds in the acyl chains). Each membrane consisting of 128 lipids and 16128 water molecules was equilibrated for 10 nanoseconds, then deformed under the equibiaxial strain state. Constant deformation velocities were applied in the x and y dimensions, while the z dimension was allowed to adjust freely under a pressure of 1 atm and a temperature of 310 K. After deformation, the failure (initial water penetration), pore nucleation and growth, and damage behavior were analyzed and compared between different lipid types.RESULTS AND CONCLUSIONSThe investigated phospholipids showed similar pore evolution and damage behavior, but significantly different failure strains - the strain at which initial water penetration happened (based on one-way ANOVA and Tukey post-hoc statistical tests with p &lt; 0.05). In general, failure happened at lower strain for the lipids with higher equilibrium area per lipid (APL). Between lipids with different headgroups, [16:0/18:1]PC had larger headgroup structure, lower lipid packing, and larger equilibrium APL (i.e. more free space in the membrane) compared to [16:0/18:1]PE. Thus, [16:0/18:1]PC was more permeable to water and had lower failure strain than [16:0/18:1]PE. Within the same PC headgroup, for each pair of lipids, Tukey test revealed that if two lipids had only one structural difference (e.g. different chain lengths in [16:0/16:1]PC, [16:0/18:1]PC and [18:0/18:1]PC, or different saturations in [16:0/18:2]PC, [16:1/18:1]PC, [16:0/18:1]PC, and [16:0/18:0]PC), their failure strains were not significantly different. However, if two lipids had more than one difference in their structures (e.g. [16:0/18:2]PC vs. [16:0/16:1]PC, in which [16:0/18:2]PC had tail-length asymmetry and two double bonds in the longer tail, while [16:0/16:1]PC had two tails with the same length and one double bond), then they exhibited significantly different failure strains ([16:0/18:2]PC had lower failure strain compared to [16:0/16:1]PC). In general, the results suggest that larger headgroup structure, more double bonds and tail-length mismatch made the phospholipids more difficult to pack against each other, increased membrane fluidity and APL, and hence lowered the failure strain. Overall, the current study provides insight on how different lipid structures affect membrane damage and mechanical failure under tensile deformation and serves as a reference for future simulations of more realistic membrane systems that include various lipid types.

Effect of Phospholipid Type on Failure and Damage of Biological Membrane Under Tension

Paper Proceedings: https://asmedigitalcollection.asme.org/IMECE/IMECE2021/volume/85543

ASME 2021 International Mechanical Engineering Congress and Exposition (IMECE2021)

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