Cell membranes and macromolecular hydration shells

Cell membranes and macromolecular hydration shells represent the fundamental structural and solvent environments that support biological life. The cell membrane is a complex lipid bilayer that serves as a semi-permeable barrier and a scaffold for membrane proteins [1]. The macromolecular hydration shell refers to the layer of water molecules immediately surrounding proteins and nucleic acids, which is critical for their folding, stability, and enzymatic activity [2]. Although not a single molecular target in the traditional sense, these environments are the site of action for several classes of drugs, including general anesthetics, which are hypothesized to exert their effects by perturbing the physical state of the membrane or the dynamics of the hydration shell [3]. Additionally, certain antimicrobial agents, such as polymyxins and polyenes, specifically target the unique lipid compositions of bacterial or fungal membranes to induce lysis and cell death [4]. The hydration shell also plays a role in drug-receptor binding, where the displacement of water molecules can drive the thermodynamics of the interaction [5]. Due to the ubiquitous nature of these structures, drugs interacting with them often face challenges related to systemic toxicity and a lack of molecular specificity. Citations: [1] Alberts B, et al. (2002) Molecular Biology of the Cell; [2] Pal SK & Zewail AH (2004) Chem Rev; [3] Franks NP (2008) Nat Rev Neurosci; [4] Hurdle JG, et al. (2011) Yale J Biol Med; [5] Bagheri A, et al. (2015) Int J Mol Sci.

Other names

Biological membranesHydration layersVicinal waterSolvation shellsLipid bilayers

Alteration of membrane fluidity, disruption of lipid packing, displacement of bound water molecules, and change in the dielectric environment of membrane-bound proteins [3][4].