Self-assembly and biophysical properties of archaeal lipids

Abstract

Archaea constitute one of the three fundamental domains of life. Archaea possess unique lipids in their cell membranes which distinguish them from bacteria and eukaryotes. This difference in lipid composition is referred to as ‘Lipid Divide' and its origins remain elusive. Chemical inertness and the highly branched nature of the archaeal lipids afford the membranes stability against extremes of temperature, pH, and salinity. Based on the molecular architecture, archaeal polar lipids are of two types — monopolar and bipolar. Both monopolar and bipolar lipids have been shown to form vesicles and other well-defined membrane architectures. Bipolar archaeal lipids are among the most unique lipids found in nature because of their membrane-spanning nature and mechanical stability. The majority of the self-assembly studies on archaeal lipids have been carried out using crude polar lipid extracts or molecular mimics. The complexity of the archaeal lipids makes them challenging to synthesize chemically, and as a result, studies on pure lipids are few. There is an ongoing effort to develop simplified routes to synthesize complex archaeal lipids to facilitate diverse biophysical studies and pharmaceutical applications. Investigation on archaeal lipids may help us understand how life survives in extreme conditions and therefore unlock some of the mysteries surrounding the origins of cellular life.

Putative roles of terpenoids in primitive membranes

“…As an example, inclusion of a DPPC derivative with branching in one tail-group at carbon position eight caused an increase in the area per lipid (APL) within the bilayer (from 0.623 to 0.668 nm 2 ), a reduction in membrane thickness (from ∼3.59 nm to ∼3.39 nm), and a decrease in the order parameter (from ∼0.2 to ∼0.1 at the branch point) (Poger et al, 2014). An unsaturated tailgroup can also fluidize the membrane, however, methyl branching has the benefit of being chemically stable under oxidative conditions (Bhattacharya, 2022). In addition to disrupting inter-chain packing, methyl branching also affects the preferred intra-chain conformation.…”

Bola-amphiphilic dendrimer empowers imatinib to target metastatic ovarian cancer stem cellsviaβ-catenin-HRP2 signaling axis

“…The copyright holder for this preprint (which this version posted June 9, 2024. ; https://doi.org/10.1101/2024.06.07.597857 doi: bioRxiv preprint the bola-amphiphilic scaffold to mimic the strong assembly properties of bola-amphiphiles found in extremophile archae bacteria [27]. To enable cancer cell-specific delivery, we incorporated a thioacetal group into our bola-amphiphilic dendrimers thus rendering them responsive to the high level of reactive oxygen species (ROS) in cancer cells [25,26].…”

“…We previously developed bola-amphiphilic poly(amidoamine) (PAMAM) dendrimers for nucleic acid delivery, comprising a hydrophobic "bola-lipid" core and two hydrophilic dendron terminals [25,26]. We designed the bola-amphiphilic scaffold to mimic the strong assembly properties of bola-amphiphiles found in extremophile archae bacteria [27]. To enable cancer cell-specific delivery, we incorporated a thioacetal group into our bola-amphiphilic dendrimers thus rendering them responsive to the high level of reactive oxygen species (ROS) in cancer cells [25,26].…”

Exploring the realm of soft matter biophysics: an early career perspective

“…A topic of long-term fascination is how biological molecules and systems can adapt to variety of conditions, including those considered extreme. Bhattacharya [8] explores this in their review on archaeal lipids, describing the 'Lipid Divide' [9] between these structures compared with lipids from bacteria and eukaryotes. This review covers how the structural differences these lipids possess impact Version of Record published: 21 December 2022 their self-assembly and biophysical properties, which could allow archaea to thrive in a vast range of environments, including the human gut.…”