Search

This review discusses main features of transmembrane (TM) proteins which distinguish them from water-soluble proteins and allow their adaptation to the anisotropic membrane environment. We overview the structural limitations on membrane protein architecture, spatial arrangement of proteins in membranes and their intrinsic hydrophobic thickness, co-translational and post-translational folding and insertion into lipid bilayers, topogenesis, high propensity to form oligomers, and large-scale conformational transitions during membrane insertion and transport function. Special attention is paid to the polarity of TM protein surfaces described by profiles of dipolarity/polarizability and hydrogen-bonding capacity parameters that match polarity of the lipid environment. Analysis of distributions of Trp resides on surfaces of TM proteins from different biological membranes indicates that interfacial membrane regions with preferential accumulation of Trp indole rings correspond to the outer part of the lipid acyl chain region—between double bonds and carbonyl groups of lipids. These “midpolar” regions are not always symmetric in proteins from natural membranes. We also examined the hydrophobic effect that drives insertion of proteins into lipid bilayer and different free energy contributions to TM protein stability, including attractive van der Waals forces and hydrogen bonds, side-chain conformational entropy, the hydrophobic mismatch, membrane deformations, and specific protein–lipid binding.

High-surface-area nanoparticles often cluster, with unknown effects on their cellular uptake and environmental impact. In the presence of vesicles or cell membranes, lipid adsorption can occur on the nanoparticles, resulting in the formation of supported lipid bilayers (SLBs), which tend to resist cellular uptake. When the amount of lipid available is in excess compared with that required to form a single-SLB, large aggregates of SLBs enclosed by a close-fitting lipid bilayer sheath are shown to form. The proposed mechanism for this process is one where small unilamellar vesicles (SUVs) adsorb to aggregates of SLBs just above the gel-to-liquid phase transition temperature, T(m) , of the lipids (as observed by dynamic light scattering), and then fuse with each other (rather than to the underlying SLBs) upon cooling below T(m) . The sacks of SLB nanoparticles that are formed are encapsulated by the contiguous close-fitting lipid sheath, and precipitate below T(m) , due to reduced hydration repulsion and the absence of undulation/protrusion forces for the lipids attached to the solid support. The single-SLBs can be released above T(m) , where these forces are restored by the free lipid vesicles. This mechanism may be useful for encapsulation/release of drugs/DNA, and has implications for the toxic effects of nanoparticles, which may be mitigated by lipid sequestration.

The Surface Forces Apparatus technique was used for measuring the adhesion, deformation, and fusion of bilayers supported on mica. The technique allows the molecular rearrangements to be followed in real time during the fusion process, and the most important forces involved to be identified. The adhesion between two bilayers can be increased by two orders of magnitude if they are thinned so as to expose more hydrophobic groups. For all the bilayer systems studied a single basic fusion mechanism was found in which the bilayers do not “overcome” the short-range repulsive steric-hydration forces; instead, local bilayer deformations allow these repulsive forces to be “bypassed”. The results further indicate that the most important force leading to the direct fusion of bilayers is the hydrophobic attraction acting between the hydrophobic interiors of bilayers (1, 2).

Properties of the biological and model membranes can be regulated by the lipid polar headgroups and their bathing solution. This occurs primarily via changes in the interfacial hydrophilicity and hydration, which are mostly a result of the lipid deprotonation or osmotic dehydration. Steric or electrostatic effects normaly play a minor role. Therefore, phosphate derivatization or protonation, further changes that decrease the lipid capacity for the hydrogen bonding and lower the interfacial affinity for binding water, as well as any system alterations that diminish the amount of interbilayer water can all cause the lipid chain melting phase transition temperature, the persistence of the lamellar lipid phase, and the colloidal stability of vesicle suspension, but also the height of the membrane permeability barrier to decrease, whereas lipid protonation or dealkylation have the reverse effect. – Lipid bilayers and their adjacent solution behave as single thermodynamic entity. Changes in the polar headgroup region and in the solvent composition consequently can regulate not only the membrane capacity for molecular or supramolecular reorganisation (e.g. phase changes or membrane fusion, respectively) but moreover may govern the short-range intermembrane (e.g. hydration) forces and, to some extent, affect the membrane-solute interactions. These effects are therefore of considerable interest and relevance for the studies and understanding of membrane binding and transport.