scholarly journals Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 802 ◽  
Author(s):  
Rumiana Tzoneva ◽  
Tihomira Stoyanova ◽  
Annett Petrich ◽  
Desislava Popova ◽  
Veselina Uzunova ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Cancer Cell ◽  
Fluorescence Correlation Spectroscopy ◽  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Membrane Lipid ◽  
Correlation Spectroscopy ◽  
Generalized Polarization ◽  
Fluorescence Correlation

Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid–lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells.

scholarly journals Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models

2020 ◽  
Author(s):  
R. Tzoneva ◽  
T. Stoyanova ◽  
A. Petrich ◽  
D. Popova ◽  
A. Momchilova ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Cancer Cell ◽  
Fluorescence Correlation Spectroscopy ◽  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Membrane Lipid ◽  
Correlation Spectroscopy ◽  
Generalized Polarization ◽  
Fluorescence Correlation

ABSTRACTAlkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, Erufosine (EPC3) is a promising drug for the treatment of several types of tumors which has not been sufficiently characterized. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy techniques (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy and generalized polarization imaging) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid-lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 might be linked to its effects on fundamental biophysical properties of lipid membranes in cancer cells.

scholarly journals Single-lipid dynamics in phase-separated supported lipid bilayers

2020 ◽  
Author(s):  
Xinxin Woodward ◽  
Christopher V. Kelly
Keyword(s):  
Lipid Bilayers ◽  
Fluorescence Correlation Spectroscopy ◽  
Cholesterol Content ◽  
Single Particle Tracking ◽  
Correlation Spectroscopy ◽  
Supported Lipid Bilayers ◽  
Membrane Composition ◽  
Fluorescence Correlation ◽  
Diffusion Rates ◽  
Lipid Diffusion

ABSTRACTPhase separation is a fundamental organizing mechanism on cellular membranes. Lipid phases have complex dependencies on the membrane composition, curvature, tension, and temperature. Single-molecule diffusion measures a key characteristic of membrane behavior and relates to the effective membrane viscosity. Lipid diffusion rates vary by up to ten-fold between liquid-disordered (Ld) and liquid-ordered (Lo) phases depending on the membrane composition, measurement technique, and the surrounding environment. This manuscript reports the lipid diffusion on phase-separated supported lipid bilayers (SLBs) with varying temperature, composition, and lipid phase. Lipid diffusion is measured by single-particle tracking (SPT) and fluorescence correlation spectroscopy (FCS) via custom data acquisition and analysis protocols that apply to diverse membranes systems. We demonstrate agreement between FCS and SPT analyses with both the single-step length distribution and the mean squared displacement of lipids with significant immobile diffusers. Traditionally, SPT is sensitive to diffuser aggregation, whereas FCS largely excludes aggregates from the reported data. Protocols are reported for identifying and culling the aggregates prior to calculating diffusion rates via SPT. With aggregate culling, all diffusion measurement methods provide consistent results. With varying membrane composition and temperature, we demonstrate the importance of the tie-line length that separates the coexisting lipid phases in predicting the differences in diffusion between the Ld and Lo phases.HIGHLIGHTSLipid diffusion varies with the lipid phases, temperature, and aggregationAggregate culling yields consistent measurements from single-particle tracking and fluorescence correlation spectroscopyMembrane with higher cholesterol content or at low temperature have more aggregatesA more variation in the diffusion rates occurred between the coexisting lipid phases at low temperatures and low cholesterol content

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