|Title||Probing Lipid Bilayers under Ionic Imbalance|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Lin, J, Alexander-Katz, A|
|Pagination||2460 - 2469|
|Keywords||atomistic molecular-dynamics, blood-cell membrane, charge imbalance, coarse-grained model, electric-fields, electroporation, force-field, gene-transfer, pore formation, single-cell|
Biological membranes are normally under a resting transmembrane potential (TMP), which originates from the ionic imbalance between extracellular fluids and cytosols, and serves as electric power storage for cells. In cell electroporation, the ionic imbalance builds up a high TMP, resulting in the poration of cell membranes. However, the relationship between ionic imbalance and TMP is not clearly understood, and little is known about the effect of ionic imbalance on the structure and dynamics of biological membranes. In this study, we used coarse-grained molecular dynamics to characterize a dipalmitoylphos-phatidylcholine bilayer system under ionic imbalances ranging from 0 to similar to 0.06 e charges per lipid (e/Lip). We found that the TMP displayed three distinct regimes: 1) a linear regime between 0 and 0.045 e/Lip, where the TMP increased linearly with ionic imbalance; 2) a yielding regime between similar to 0.045 and 0.060 e/Lip, where the TMP displayed a plateau; and 3) a poration regime above similar to 0.060 e/Lip, where we observed pore formation within the sampling time (80 ns). We found no structural changes in the linear regime, apart from a nonlinear increase in the area per lipid, whereas in the yielding regime the bilayer exhibited substantial thinning, leading to an excess of water and Na+ within the bilayer, as well as significant misalignment of the lipid tails. In the poration regime, lipid molecules diffused slightly faster. We also found that the fluid-to-gel phase transition temperature of the bilayer dropped below the normal value with increased ionic imbalances. Our results show that a high ionic imbalance can substantially alter the essential properties of the bilayer, making the bilayer more fluid like, or conversely, depolarization of a cell could in principle lead to membrane stiffening.
|Short Title||Biophys. J.|