Liquid but Durable: Molecular Dynamics Simulations Explain the Unique Properties of Archaeal-Like Membranes

OPEN SUBJECT AREAS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS COMPUTATIONAL BIOPHYSICS Liquid but Durable: Molecular Dynamics Simulations Explain the Unique Properties of Archaeal-Like Membranes Anton O. Chugunov1, Pavel E. Volynsky1, Nikolay A. Krylov1,2, Ivan A. Boldyrev1 & Roman G. Efremov1,3,4 MEMBRANE BIOPHYSICS 1 Received 8 September 2014 Accepted 24 November 2014 Published 12 December 2014 Correspondence and requests for materials should be addressed to A.O.C. (batch2k@ yandex.ru) M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya, 16/ 10, Moscow 117997, 2Joint Supercomputer Center, Russian Academy of Sciences, Leninsky prospect, 32a, Moscow 119991, Russia, 3Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, 141700, Russia, 4Higher School of Economics, Myasnitskaya ul. 20, 101000 Moscow, Russia. Archaeal plasma membranes appear to be extremely durable and almost impermeable to water and ions, in contrast to the membranes of Bacteria and Eucaryota. Additionally, they remain liquid within a temperature range of 0–1006C. These are the properties that have most likely determined the evolutionary fate of Archaea, and it may be possible for bionanotechnology to adopt these from nature. In this work, we use molecular dynamics simulations to assess at the atomistic level the structure and dynamics of a series of model archaeal membranes with lipids that have tetraether chemical nature and ‘‘branched’’ hydrophobic tails. We conclude that the branched structure defines dense packing and low water permeability of archaeal-like membranes, while at the same time ensuring a liquid-crystalline state, which is vital for living cells. This makes tetraether lipid systems promising in bionanotechnology and material science, namely for design of new and unique membrane nanosystems. A rchaea are microorganisms that thrive predominantly in extreme conditions (very high/low temperatures, high pressure, acidity and/or salinity), although many of them inhabit more ‘‘common’’ econiches (ocean water, soil, intestine, etc)1. According to pioneering works by Carl Woese, Archaea are a group apart not only ecologically, but also evolutionary2,3, nowadays designated as the third domain of life (along with Bacteria and Eucaryota). One hypothesis suggests that the separation of Bacteria and Archaea resulted from the individualization of membranes, which were ‘‘promiscuous’’ in the Last Universal Common Ancestor (LUCA) and became more specialized in the two modern domains of microorganisms due to the so-called ‘‘Lipid Divide’’ ancient event4. There are two major differences in membrane lipids structure between Archaea and Bacteria: 1) glycerol backbone chirality and the way the hydrophobic ‘‘tails’’ are connected, and 2) the chemical nature of these tails. In Bacteria and Eucaryota, straight fatty acid acyl chains are linked by ester bonds to sn-1 and sn-2 positions of glycerol, while in Archaea, branched isoprenoid hydrocarbon chains are bound by ether bonds to sn-2 and sn-3 glycerol positions5. Glycerol backbones are enantiomers in both Bacteria and Archaea. The polar heads used are also often different, although they are not unique to any domain of life. Of the two aforementioned chemical differences between bacterial and archaeal lipids, glycerol chirality may have played a very important evolutionary role4,6, although it most probably does not affect the physical properties of the membranes. In contrast, the primordially branched isoprenoid chains in Archaea are likely to determine the very dense packing7,8, high membrane viscosity9 and durability10 and low permeability to water and ions, which are the main characteristics of archaeal membranes compared with bacterial or eukaryotic ones11–13. An additional modification that increases the density of packing and decreases membrane permeability is cyclopentane rings in the hydrophobic tails, which are encountered more often in acidophilic microorganisms7,14. Moreover, Archaea are able to adapt their membranes to better fit their growth conditions5,15, employing several types of lipids’ structure variation. Finally, most hyperthermophiles contain lengthy C40-based glycerol-dialkylglyceroltetraether (GDGT) lipids, which are usually referred to as caldarchaeols or bolalipids16 and represent ‘‘tail-to-tail’’ linked glycerol-dialkyl-glyceroldiether (GDGD) lipids, or archaeols. This modification provides extra durability for the membranes by switching from a bilayer to a more rigid monolayer structure. In spite of these extraordinary mechanical properties reminiscent of a gel state of ‘‘conventional’’ dipalmitoylphosphatidylcholine (DPPC)8, archaeal membranes may be considered liquid crystalline within a very broad temperature range (0–1001uC)17,18, which is believed to be vital for each living cell. At the same time, very high SCIENTIFIC REPORTS | 4 : 7462 | DOI: 10.1038/srep07462 1 www.nature.com/scientificreports durability and liquidity seem to be the most fundamental physical properties of archaeal membranes. This not only provides an insight into the evolutionary fate of Archaea, but may also be adopted by bionanotechnology in order to design new unique materials19. In order to achieve this, a detailed understanding of the physico-chemical properties of such membranes is required. In contrast to ‘‘common’’ bilayer membranes, archaeal membranes are monolayers, and the organization of their nonpolar core can strongly depend on the occurrence of various branching groups in the tetraether lipids. Experimental investigations in this field are hindered by the complex mixture of lipid extracts from archaeal membranes and the complexity of the chemical synthesis of the GDGT lipids. Hence, computer experiments may help provide relevant information with regards to the microscopic organization of such membranes. Although this task is within reach of modern computational methods, only a few research papers have been published in this field. The most important work is by Bulacu et al.20, who performed a molecular dynamics (MD) simulation of a bolalipid membrane in order to find out the effect of lipids’ tail linkage. However, due to the coarsegrained representation used, the role of branching methyl and cyclopentane groups could hardly be assessed, although the authors provide some insights into the phase condition and design of synthetic durable membranes. In their early work, Gabriel & Chong21 assessed via MD the role of cyclopentane rings in the tight packing of the membrane, although they did not systematically address the influence of branched methyl groups. Another work has shown the effect of tail linkage in archaeal lipids: expectedly, tetraether lipids exhibit lower lateral diffusion compared with diether ones22. The second issue to be carefully considered is the juxtaposition of the atomistic-scale properties of membranes compos (...truncated)