Search

Nucleotides, amino acids, sugars, and lipids are almost ubiquitously homochiral within individual cells on Earth. While oligonucleotides and proteins exist as one natural chirality throughout the tree of life, two stereoisomers of phospholipids have separately emerged in archaea and bacteria, an evolutionary divergence known as "the lipid divide". Within this review, we focus on the emergence of phospholipid homochirality and compare the stability of synthetic homochiral and heterochiral membranes in vitro. We discuss chemical probes designed to study the stereospecific interactions of lipid membranes in vitro. Overall, we aim to highlight studies that help elucidate the determinants of stereospecific interactions between lipids, peptides, and small molecule ligands. Continued work in understanding the drivers of favorable interactions between chiral molecules and biological membranes will lead to the design of increasingly selective chemical tools for bioorthogonal labeling of lipid membranes and safer membrane-associating pharmaceuticals.

Three-dimensional (3D) models are essential for visualization and conceptual understanding of complex architectures such as protein structure. Although there is a plethora of software platforms that allow digital depictions of protein structure at an atomic level in silico, physical models are needed to convey an intuitive understanding of biomolecular architecture. However, it is a challenge to represent all the relevant features of proteins in a single physical model due to their sheer structural complexity. Here, we describe a modular protein model that focuses only on representation of the secondary structure - the underlying structural skeleton. The simplified model consists of amino acid units, which can be linked together to reproduce the two most fundamental structural features of protein secondary structure: the relative positions of the amino acid alpha carbon atoms, and the intra-main chain hydrogen bonding pattern. We use 3D printing and magnets to create a set of three modular amino acid building blocks, which when linked together into a chain, can faithfully represent alpha helices, beta sheets, and turns. These simple to make models can be used to quickly assemble the alpha carbon trace of an entire protein domain, which conveys a tactile experience of the complexity of protein skeletal architecture. These models highlight the modularity of protein structure: where a single structural unit, the amino acid, can be linked together to form a larger, regular secondary structure. These models also have a propensity to spontaneously organize into alpha helices and beta sheets, as demonstrated by their ability to autonomously assemble when placed in a circulating water tank. These models provide a missing educational tool to expand knowledge of protein structure, foster deeper insight into protein folding, and inspire greater interest in biomacromolecular architecture.