Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors

Transplantation of rod photoreceptors, derived either from neonatal retinae or pluripotent stem cells (PSCs), can restore rod-mediated visual function in murine models of inherited blindness. However, humans depend more upon cone photoreceptors that are required for daylight, color, and high-acuity vision. Indeed, macular retinopathies involving loss of cones are leading causes of blindness. An essential step for developing stem cell-based therapies for maculopathies is the ability to generate transplantable human cones from renewable sources. Here, we report a modified 2D/3D protocol for generating hPSC-derived neural retinal vesicles with well-formed ONL-like structures containing cones and rods bearing inner segments and connecting cilia, nascent outer segments, and presynaptic structures. This differentiation system recapitulates human photoreceptor development, allowing the isolation and transplantation of a pure population of stage-matched cones. Purified human long/medium cones survive and become incorporated within the adult mouse retina, supporting the potential of photoreceptor transplantation for treating retinal degeneration

Water and Salt at the Lipid-Solvent Interface

Lipid bilayers are important biological structures. The changes in bilayer properties are induced by the composition of the bilayer as well as the solvent. In this work, we study the effects of different molecular makeups of lipids and ionic solvents with molecular dynamics simulations to determine their effect on the bilayer interface. In particular, we look at how different carbon chain bindings affect water viscosity at the interface and allow for a less permeable bilayer. Additionally, we examine the changes to the bilayer due to the presence of the most biologically relevant salt ions. Lastly, we show how the pharmacological ion lithium may replace magnesium due to overlapping solvation shells

A Statistical Mechanical Model of Proteoglycan-Collagen Fibrils

Proteoglycans play a key role in fibril organization. Proteoglycans bind to the surfaces of collagen fibrils affecting their arrangement. A statistical model was constructed to determine the thermodynamics of proteoglycan-connected collagen fibrils that can be used to understand the formation of collagenous tissues. This model was found to be similar to a clock model. A Metropolis Monte-Carlo algorithm generated sample states of the collagen fibrils for different densities of proteoglycan, at different temperatures. Heat capacities, energies, displacements, and other properties were calculated from these states.The data show areas of interest and a possible phase transition at different temperatures depending on the density

Effects of Lithium and Other Monovalent Ions on Palmitoyl Oleoyl Phosphatidylcholine Bilayer

Interactions of monovalent salts with lipid membranes are explored with molecular dynamics (MD) simulations. The simulations included the monovalent ions Na⁺ and K⁺, for their importance in physiology, Li⁺ for its small size and importance in several medical conditions including bipolar disorder, and Rb⁺ for its large size. All simulations included Cl^– as counterions. One bilayer was simulated without salt as a control. Palmitoyl oleoyl phosphatidylcholine (POPC) bilayers experienced reductions in area per lipid with the addition of salt; the smaller the ion the smaller the area, with the exception of Li⁺. Li⁺ exhibited unique binding affinities between phosphates and <i>sn</i>-2 carbonyls that lowered the order of the top part of <i>sn</i>-2 chain, which increased the area per lipid, compared to other ionic simulations. Further, we observe that monovalent salts alter bilayer properties through structural changes and not so much through the changes in surface potential