Phospholipases and Membrane Curvature: What Is Happening at the Surface?

Abstract

In this revision work, we emphasize the close relationship between the action of phospholipases and the modulation of membrane curvature and curvature stress resulting from this activity. The alteration of the tridimensional structure of membranes upon the action of phospholipases is analyzed based on studies on model lipid membranes. The transient unbalance of both compositional and physical membrane properties between the hemilayers upon phospholipase activity lead to curvature tension and the catalysis of several membrane-related processes. Several proteins’ membrane-bound and soluble forms are susceptible to regulation by the curvature stress induced by phospholipase action, which has important consequences in cell signaling. Additionally, the modulation of membrane fusion by phospholipase products regulates membrane dynamics in several cellular scenarios. We commented on vesicle fusion in the Golgi-endoplasmic system, synaptic vesicle fusion to the plasma membrane, viral membrane fusion to host cell plasma membrane and gametes membrane fusion upon acrosomal reaction. Furthermore, we explored the modulation of membrane fusion by the asymmetric adsorption of amphiphilic drugs. A deep understanding of the relevance of lipid membrane structure, particularly membrane curvature and curvature stress, on different cellular events leads to the challenge of its regulation, which may become a powerful tool for pharmacological therapy.

Multidimensional Spectral Phasors of LAURDAN’s Excitation–Emission Matrices: The Ultimate Sensor for Lipid Phases?

“…For these compositions, the formation of inverse nonlamellar structures is expected due to the reduction of the polar headgroup of the lipids. These reactions are very well documented, ,− and here, we corroborated their occurrence by observing an increase in the particle diameter of the self-assembled lipid structures by dynamic light scattering measurements (Figure S16). Figure C displays the ternary diagrams for the MdSP of each case, Figure S17 shows the EEMs obtained, Figure S18 depicts individual representations of the excitation and emission spectra, and Figure S19 summarizes their respective phasors’ plot.…”

“…This red shift of LAURDAN in GMO interfaces was already reported in a recent work . Cubic phases exhibit zero main curvature and a negative Gaussian curvature, indicating that the two radii cancel each other. , Therefore, although its surface exhibits faster water rotation and a larger extent of relaxation, this configuration is not expected to be too far from lamellar structures, as confirmed by the MdSP in Figure A. On the other hand, moving downward to the RR corner, there is more excitation at the red band, implying a high probability of finding the probe stabilized by surrounding solvent dipoles.…”

“…This result is consistent with a less-hydrated and morestructured interface, as expected for the nonlamellar product obtained by the action of both enzymes. 3,40 ■ CONCLUSIONS With the conceptual framework presented in this work, we think that the topological organization of the regions in Figure 4 can offer a reasonable approximation of a lipid phase map, as observed by the LAURDAN probe. Our hypothesis has been evaluated through measurements of well-established conditions, resulting in strong confirmation.…”

“…In addition, we also explored enzymatically induced lamellar to nonlamellar transition, particularly for two phospholipases: PLC and SMase. These enzymes are known to disrupt lamellar structures by affecting the geometrical properties of their lipid substrates (i.e., their packing parameter), provoking changes in their self-assembled structures. ,− This variation is reflected as a global increase from nano to microsize particle populations (Figure S16) as well as in their interfacial properties. LAURDAN is also sensitive to these changes, depicting not only a remarkable blueshift on its emission but also with striking effects on its excitation profile (Figure S18).…”

“…The study of the physical state of lipid assemblies is important for understanding biological processes occurring at membrane interfaces, such as catalysis, signal transduction, membrane rearrangements, etc. A wide range of techniques can be used for these studies, both for model and cellular membranes. − A very common approach is the use of fluorescence probes that are responsive to various membrane properties, like lateral or rotational diffusion, fluidity, hydration, and permeability. , The specific fluorescence technique to use (steady-state spectroscopy, lifetime measurement, anisotropy, or quenching) will depend on both the photophysics of the molecule and the phenomenon of interest. , LAURDAN is a fluorescent membrane probe that has a 6-dimethylamine-2-naphthalenyl core, belonging to the family of DAN fluorophores introduced by Gregorio Weber in the late 1970s . His original design included an electron donor and an electron acceptor group strategically positioned at opposite ends of the naphthalene ring.…”