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Organotin compounds, being biologically active, affect a variety of cellular functions due to their ability to accumulate in and penetrate biological membranes. These compounds influence the distribution of electrostatic charges, alter organization, disrupt molecular dynamics and change mechanical properties of biological membranes. It was found that the membrane/water partition coefficient equals 4, a value significantly higher than octanol/water partition coefficient. In addition, the effect of di- and tri-phenyltin chlorides on the mechanics of model lipid membranes was measured for the first time. It has been determined that phenyltins affect the global model lipid bilayer properties by reducing the membrane expansion modulus, when measured using micromanipulation technique, and elevating the bending rigidity coefficient of the lipid bilayer, as determined with the flickering noise spectroscopy. In addition, the elevated water permeability shows that phenyltins also cause the local defects formation in the lipid bilayer, i.e. lipid pores. These data shows that phenyltins may interfere indirectly with variety cellular processes by altering non-specifically the entire cellular membrane system. Accordingly, when phenyltins are added to macrophages in culture, they inflict massive alterations of cell morphology and interfere with membrane-associated processes, as visualized using fluorescence labelling of selected subcellular compartments., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The major component of the cell membrane skeleton, spectrin, is anchored in the cell membrane via interactions with membrane proteins. It has been previously shown that both erythroid and non-erythroid spectrin interact directly with membrane phospholipids (mainly aminophospholipids). One of the binding sites responsible for these interactions is located in the ankyrin-binding domain. In the present study, in order to better understand the character of binding, a more detailed investigation of the interactions between the beta-spectrin fragments corresponding to the truncated mutants of the ankyrin-binding domain (Frag1 and Frag3) and liposomes of different compositions were carried out. The obtained results suggest that the binding of both spectrin fragments with liposomes induces conformational changes within the protein. Analysis of the changes in intrinsic tryptophan fluorescence spectra upon binding with liposomes, together with quenching studies (from the water and membrane hydrocarbon environment), allows for qualitative description of changes in proteins conformation. Our results suggest that the largest conformational changes occur for Frag1 bound to PC : PE (2 : 3) liposomes what is consistent with previous studies on monolayers. They are also in good agreement with those obtained previously for native erythroid and nonerythroid spectrin molecules.

Medin, a recently discovered 5.5 kDa peptide, is associated with amyloid deposits in the medial layer of human arteries and the prevalence is nearly 100% within individuals above 50 years. Presently, not much is known about its biochemical and biophysical properties or its pathway from soluble peptide to insoluble amyloid. Here we have characterized the behavior of medin in the presence of lipid membranes, using circular dichroism, isothermal titration calorimetry, differential scanning calorimetry, size exclusion chromatography, and atomic force microscopy (AFM). Medin was shown to exist as a monomer in solution with a predominantly random-coil structure. It binds lipid vesicles that have either a neutral or a negative surface potential. Upon association to membranes containing acidic lipids, it undergoes an electrostatically driven conformational change towards a mainly alpha-helical state. Prolonged incubation converts medin from an alpha-helical structure into an amyloid beta-sheet fibrillar state as confirmed by AFM. Based on these findings, we propose a mechanism of medin-amyloid formation where medin electrostatically associates in its monomeric form to biological interfaces displaying a negative potential. This process both increases the local peptide concentration and induces an aggregation-prone alpha-helical fold.