Stability of MultiComponent Biological Membranes

Equilibrium equations and stability conditions are derived for a general class of multicomponent biological membranes. The analysis is based on a generalized Helfrich energy that accounts for geometry through the stretch and curvature, the composition, and the interaction between geometry and composition. The use of nonclassical differential operators and related integral theorems in conjunction with appropriate composition and mass conserving variations simplify the derivations. We show that instabilities of multicomponent membranes are significantly different from those in single component membranes, as well as those in systems undergoing spinodal decomposition in flat spaces. This is due to the intricate coupling between composition and shape as well as the nonuniform tension in the membrane. Specifically, critical modes have high frequencies unlike single component vesicles and stability depends on system size unlike in systems undergoing spinodal decomposition in flat space. An important implication is that small perturbations may nucleate localized but very large deformations. We show that the predictions of the analysis are in qualitative agreement with experimental observations

Shapes of pored membranes

We study the shapes of pored membranes within the framework of the Helfrich theory under the constraints of fixed area and pore size. We show that the mean curvature term leads to a budding- like structure, while the Gaussian curvature term tends to flatten the membrane near the pore; this is corroborated by simulation. We propose a scheme to deduce the ratio of the Gaussian rigidity to the bending rigidity simply by observing the shape of the pored membrane. This ratio is usually difficult to measure experimentally. In addition, we briefly discuss the stability of a pore by relaxing the constraint of a fixed pore size and adding the line tension. Finally, the flattening effect due to the Gaussian curvature as found in studying pored membranes is extended to two-component membranes. We find that sufficiently high contrast between the components' Gaussian rigidities leads to budding which is distinct from that due to the line tension.Comment: 8 pages, 9 figure

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

Digital Holographic Microscopy of Phase Separation in Multicomponent Lipid Membranes

Lateral in-homogeneities in lipid compositions cause microdomains formation and change in the physical properties of biological membranes. With the presence of cholesterol and mixed species of lipids, phospholipid membranes segregate into lateral domains of liquid-ordered and liquid-disordered phases. Coupling of two-dimensional intralayer phase separations and interlayer liquid-crystalline ordering in multicomponent membranes has been previously demonstrated. By the use of digital holographic microscopy (DHMicroscopy), we quantitatively analyzed the volumetric dynamical behavior of such membranes. The specimens are lipid mixtures composed of sphingomyelin, cholesterol, and unsaturated phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine. DHMicroscopy in a transmission mode is an effective tool for quantitative visualization of phase objects. By deriving the associated phase changes, three-dimensional information on the morphology variation of lipid stacks at arbitrary time scales is obtained. Moreover, the thickness distribution of the object at demanded axial planes can be obtained by numerical focusing. Our results show that the volume evolution of lipid domains follows approximately the same universal growth law of previously reported area evolution. However, the thickness of the domains does not alter significantly by time; therefore, the volume evolution is mostly attributed to the changes in area dynamics. These results might be useful in the field of membrane-based functional materials

Nanoporous silica-based protocells at multiple scales for designs of life and nanomedicine.

Various protocell models have been constructed de novo with the bottom-up approach. Here we describe a silica-based protocell composed of a nanoporous amorphous silica core encapsulated within a lipid bilayer built by self-assembly that provides for independent definition of cell interior and the surface membrane. In this review, we will first describe the essential features of this architecture and then summarize the current development of silica-based protocells at both micro- and nanoscale with diverse functionalities. As the structure of the silica is relatively static, silica-core protocells do not have the ability to change shape, but their interior structure provides a highly crowded and, in some cases, authentic scaffold upon which biomolecular components and systems could be reconstituted. In basic research, the larger protocells based on precise silica replicas of cells could be developed into geometrically realistic bioreactor platforms to enable cellular functions like coupled biochemical reactions, while in translational research smaller protocells based on mesoporous silica nanoparticles are being developed for targeted nanomedicine. Ultimately we see two different motivations for protocell research and development: (1) to emulate life in order to understand it; and (2) to use biomimicry to engineer desired cellular interactions