Asymmetry and Rippling in Mixed Surfactant Bilayers from All-Atom and Coarse-Grained Simulations: Interdigitation and Per Chain Entropy

Abstract

Understanding lateral organizations of self-assembled bilayers is crucial to gain a control on functionally relevant topologies. We study self-assembled bilayers composed of a surfactant, behenyl trimethyl ammonium chloride (BTMAC), a cosurfactant, stearyl alcohol (SA), at a ratio of 2:1 in the presence of water at 283 K employing subsequent all-atom (AA) and coarse-grained (CG) molecular dynamics simulations. Differences in initial configurations lead to the formation of bilayers at ripple or square phases or interdigitated gel phases of varying trans-leaflet asymmetry. The AA ripple and gel phases are reproduced well at the CG level using bonded potentials from Boltzmann inversion of AA canonical sampling and nonbonded potentials from MARTINI. Inhomogeneous populations of disordered chains with higher per chain configurational entropy and tilt result in rippling stabilized by periodic hydrophobic energy barrier and strong interdigitation. Order parameters of the asymmetric bilayers are sufficiently coupled to the per chain entropies at both levels of resolutions to serve as a reflector of the per chain configurational entropy inaccessible by experiments. Thus, trans-bilayer asymmetry may be a controlling parameter to induce rippling in a bilayer of industrial importance. This work will be useful for future investigation on domain-associated transport and signaling in biomembranes at a low temperature.

Evaluating Coarse-Grained MARTINI Force-Fields for Capturing the Ripple Phase of Lipid Membranes

“…Molecular simulations at various levels of FF descriptions, ranging from all-atom and united atom models at the finer scales to DPD and MARTINI models at higher levels of coarse graining, have been extensively used to study the rich variety of equilibrium phases observed in model phospholipid bilayer membranes 1,17,76 . In particular, the rippled phase, sensitive to initial configurations, annealing protocols, and finite-size effects, has been challenging to capture using MD simulations 20,25,34,41 . Although all-atom FFs have successfully captured the formation of the ripple phase (Table 1), the ability of the widely used MARTINI force-fields to stabilize this intermediate phase, which occurs below the main gel-to-liquid crystalline transition, has been a matter of some debate 34,47 .…”

“…43 BTMAC+SA 2020 All-atom, coarse-grained CHARMM36, MARTINI -Ref. 25 Abbreviations: DPD -dissipative particle dynamics; DPPC -1,2-dipalmitoyl-sn-glycero-3-phosphocholine; DMPC -1,2-dimyristoyl-sn-glycero-3-phosphocholine; BTMAC -benzyltrimethylammonium chloride; SA -stearyl alcohol.…”

“…S1a). Voronoi-thickness membrane maps, which are Voronoi diagrams of the upper membrane leaflet superimposed onto P-P thickness heatmaps 25,41 , are shown in Fig. 1d, corresponding to the top views of MD snapshots in Fig.…”

“…Thus, MARTINI FF parameters may have to be tuned to reproduce the lipid membrane phase diagram, in particular the phase, more accurately. FF approaches that tune the bonded parameters of MARTINI lipids based on comparison with allatom simulations 25,30,34 may result in models that better capture membrane phase behaviour. Fig.…”

“…At higher temperatures, DPPC exhibits a main to phase transition, with the phase occurring at pre-transition temperatures [32][33][34][35][36][37][38] . The phase has interesting properties such as the influence of thermal history on the symmetry of the ripple domains 20 , and therefore has been the subject of extensive experimental 33,[37][38][39][40] and theoretical [18][19][20][21]25,30,35,36,[41][42][43][44][45] studies. In Table 1, we summarize some of the previous studies where the rippled phase has been observed, including details of lipid type, resolution (all-atom, united atom or coarse-grained) and FF.…”