Cyclopentane rings in hydrophobic chains of a phospholipid enhance the bilayer stability to electric breakdown

• Published in: Soft matter 2020-04, Vol.16 (13), p.3216-3223
• Main Authors: Batishchev, Oleg V, Alekseeva, Anna S, Tretiakova, Daria S, Galimzyanov, Timur R, Chernyadyev, Andrey Yu, Onishchenko, Natalia R, Volynsky, Pavel E, Boldyrev, Ivan A
• Format: Article
• Language: English
• Subjects: Archaea; Bending modulus; Calcein; Chain mobility; Computer simulation; Covalent bonds; Cyclopentane; Electrical faults; Extreme environments; Fluorescence; Hydrocarbons; Hydrophobicity; Lecithin; Lipid membranes; Lipids; Liposomes; Membranes; Mobility; Molecular chains; Molecular conformation; Molecular dynamics; Phosphatidylcholine; Phospholipids; Room temperature; Stability; Stiffness
• ISSN: 1744-683X; 1744-6848
• DOI: 10.1039/c9sm02001b

Archaeal lipids ensure unprecedented stability of archaea membranes in extreme environments. Here, we incorporate a characteristic structural feature of an archaeal lipid, the cyclopentane ring, into hydrocarbon chains of a short-chain (C12) phosphatidylcholine to explore whether the insertion would allow such a lipid (1,2-di-(3-(3-hexylcyclopentyl)-propanoate)- sn-glycero -3-phosphatidylcholine, diC12cp-PC ) to form stable bilayers at room temperature. According to fluorescence-based assays, in water diC12cp-PC formed liquid-crystalline bilayers at room temperature. Liposomes produced from diC12cp-PC retained calcein for over a week when stored at +4 °C. diC12cp-PC could also form model bilayer lipid membranes that were by an order of magnitude more stable to electrical breakdown than egg PC membranes. Molecular dynamics simulation showed that the cyclopentane fragment fixes five carbon atoms (or four C-C bonds), which is compensated by the higher mobility of the rest of the chain. This was found to be the reason for the remarkable stability of the diC12cp-PC bilayer: restricted conformational mobility of a chain segment increases the membrane bending modulus (compared to a normal hydrocarbon chain of the same length). Here, higher stiffness practically does not affect the line tension of a membrane pore edge. Rather it makes it more difficult for diC12cp-PC to rearrange in order to line the edge of a hydrophilic pore; therefore, fewer pores are formed. Bilayers of a phospholipid with cyclopentane-containing chains are stable to pore formation due to restricted conformational mobility of the chains and inability of the molecules to rearrange in order to line the edge of a hydrophilic pore.