We investigate the behavior of two-dimensional systems that exhibit a transition between homogeneous and spatially inhomogeneous phases, which have spherical topology, and whose mechanical properties depend on the local value of the order parameter. One example of such a system is multicomponent lipid bilayer vesicles, which serve as a model to study cellular membranes. Under certain conditions, such bilayers separate into coexisting liquid-ordered and liquid-disordered regions. When arranged into the shape of small vesicles, this phase coexistence can result in spatial patterns that are more complex than the basic two-domain configuration encountered in typical bulk systems. The difference in bending rigidity between the liquid-ordered and liquid-disordered regions couples the shape of the vesicle to the local composition. We show that this interplay gives rise to a rich phase diagram that includes homogeneous, separated, and axisymmetric modulated phases that are divided by regions of spiral patterns in the surface morphology.
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http://dx.doi.org/10.1063/5.0020087 | DOI Listing |
J Phys Chem B
January 2025
Department of Chemistry, University of Tennessee, Knoxville, Tennessee 37916, United States.
Eukaryotic plasma membranes exhibit nanoscale lateral lipid heterogeneity, a feature that is thought to be central to their function. Studying these heterogeneities is challenging since few biophysical methods are capable of detecting domains at submicron length scales. We recently showed that cryogenic electron microscopy (cryo-EM) can directly image nanoscale liquid-liquid phase separation in extruded liposomes due to its ability to resolve the intrinsic thickness and electron density differences of ordered and disordered phases.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
PASTEUR, Department of Chemistry, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, 75005, Paris, France.
Giant unilamellar vesicles (GUVs) are widely used minimal cell models where essential biological features can be reproduced, isolated and studied. Although precise spatio-temporal distribution of membrane domains is a process of crucial importance in living cells, it is still highly challenging to generate anisotropic GUVs with domains at user-defined positions. Here we describe a novel and robust method to control the spatial position of lipid domains of liquid-ordered (Lo)/liquid-disordered (Ld) phase in giant unilamellar vesicles.
View Article and Find Full Text PDFEur J Pharm Sci
February 2025
Departamento de Química e Bioquímica, Faculdade de Ciências, Centro de Química Estrutural, Institute of Molecular Sciences, Universidade de Lisboa, Campo Grande 1749-016, Portugal. Electronic address:
Tuberculosis is one of the leading causes of mortality worldwide due to the growth of multi-drug resistant strains unsusceptible to currently available therapies. Four compounds, isoniazid (INH) and three derivatives, N'-decanoylisonicotinohydrazide (INHC10), N'-(E)-(4-phenoxybenzylidene)isonicotinohydrazide (N34) and N'-(4-phenoxybenzyl)isonicotinohydrazide (N34red), were studied. Owing to their advantageous in vitro selectivity index against the primary mutation responsible for drug resistance in Mycobacterium tuberculosis (Mtb), as well as their suitable lipophilicity and interaction with human serum albumin, INHC10 and N34 were deemed promising antitubercular compounds.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Department of Biomedical Engineering, Ben Gurion University of the Negev, Be'er Sheva 84105, Israel.
Many ternary mixtures composed of saturated and unsaturated lipids with cholesterol (Chol) exhibit a region of coexistence between liquid-disordered (Ld) and liquid-ordered (Lo) domains, bearing some similarities to lipid rafts in biological membranes. However, biological rafts also contain many proteins that interact with the lipids and modify the distribution of lipids. Here, we extend a previously published lattice model of ternary DPPC/DOPC/Chol mixtures by introducing a small amount of small proteins (peptides).
View Article and Find Full Text PDFBiophys J
December 2024
Department of Physics & Astronomy, University of Delaware, Newark, Delaware; Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware. Electronic address:
Experimental studies of collective dynamics in lipid bilayers have been challenging due to the energy resolution required to observe these low-energy phonon-like modes. However, inelastic x-ray scattering (IXS) measurements-a technique for probing vibrations in soft and biological materials-are now possible with sub-meV resolution, permitting direct observation of low-energy, phonon-like modes in lipid membranes. Here, IXS measurements with sub-meV energy resolution reveal a low-energy optic-like phonon mode at roughly 3 meV in the liquid-ordered (L) and liquid-disordered phases of a ternary lipid mixture.
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