Vesicular and Planar Membranes of Archaea Lipids: Unusual Physical Properties and Biomedical Applications

Abstract

Liposomes and planar membranes made of archaea or archaea-like lipids exhibit many unusual physical properties compared to model membranes composed of conventional diester lipids. Here, we review several recent findings in this research area, which include (1) thermosensitive archaeosomes with the capability to drastically change the membrane surface charge, (2) MthK channel's capability to insert into tightly packed tetraether black lipid membranes and exhibit channel activity with surprisingly high calcium sensitivity, and (3) the intercalation of apolar squalane into the midplane space of diether bilayers to impede proton permeation. We also review the usage of tetraether archaeosomes as nanocarriers of therapeutics and vaccine adjuvants, as well as the biomedical applications of planar archaea lipid membranes. The discussion on archaeosomal therapeutics is focused on partially purified tetraether lipid fractions such as the polar lipid fraction E (PLFE) and glyceryl caldityl tetraether (GCTE), which are the main components of PLFE with the sugar and phosphate removed.

Keywords: archaea; archaeosomes; biosensing; black lipid membranes; coating; controlled release; diethers; drug delivery; planar membranes; tetraether lipids.

Figure 1

Illustration of structures of tetraether lipids in the polar lipid fraction E (PLFE) extracted from the thermoacidophilic archaeon S. acidocaldarius. PLFE contains two components: (a) GDGT and (b) GDNT. Each has two polar headgroups with one being phospho-myo-inositol (R1). The other polar head group is either glycerol-linked β-D-galactosyl-D-glucose (GDGT R2) or calditol-linked β-D-glucose (GDNT R2). Each dibiphytanyl chain may contain 0–8 cyclopentene rings. In this illustration, zero and four cyclopentane rings are present in the dibiphytanyl chain for GDGT and GDNT, respectively. Modified from [16].

Figure 2

(Left) Structures of diether lipids in the polar lipid methanol fraction (PLMF) extracted from the hyperthermophile Aeropyrum pernix. (Right) Putative membrane structure containing AI (blue circles), AGI (red circles), and the apolar molecule squalane, which resides in the mid-plane space of diether bilayers, similar to the case of squalane in DoPhPC as revealed by neutron diffraction [21,22,23,24,25].

Figure 3

Thermosensitive archaeosomes made of PLFE and DPPC (molar ratio 3:7) exhibit unusual physical properties. (A) zeta potential of this formulation undergoes a dramatic change from very negative at and below the body temperature to much less negative at 44 °C. (B) In conjunction with this temperature jump and zeta potential change, there is an abrupt increase of the rate of drug release from the archaeosomes. (C) The plausible explanations of the zeta potential change involve major archaeosomal structural changes such as DPPC melting, PLFE flip-flop, domain segregation due to hydrophobic mismatch [90], polar headgroup exposure [91], etc. (A,B) are taken from [16] with permission.

Figure 4

Proposed Mthk behaviors in (A) BLM_PLFE versus (B) BLM_diester in a microfluidic chamber based on the findings shown in [113]. The blue and red protein structures represent the positions of Glu-92 and Glu-96, respectively, within the MthK channel [122].