Correlating biological activity to thermo-structural analysis of the interaction of CTX with synthetic models of macrophage membranes

Abstract

The important pharmacological actions of Crotoxin (CTX) on macrophages, the main toxin in the venom of Crotalus durissus terrificus, and its important participation in the control of different pathophysiological processes, have been demonstrated. The biological activities performed by macrophages are related to signaling mediated by receptors expressed on the membrane surface of these cells or opening and closing of ion channels, generation of membrane curvature and pore formation. In the present work, the interaction of the CTX complex with the cell membrane of macrophages is studied, both using biological cells and synthetic lipid membranes to monitor structural alterations induced by the protein. Here we show that CTX can penetrate THP-1 cells and induce pores only in anionic lipid model membranes, suggesting that a possible access pathway for CTX to the cell is via lipids with anionic polar heads. Considering that the selectivity of the lipid composition varies in different tissues and organs of the human body, the thermostructural studies presented here are extremely important to open new investigations on the biological activities of CTX in different biological systems.

Lamellarity-Driven Differences in Surface Structural Features of DPPS Lipids: Spectroscopic, Calorimetric and Computational Study

“…Regarding the DSC curve of ( Figure 2 d), the first thing that catches the eye is the great uncertainty in melting profile of LUV, but exclusively at the high-temperature wing of the curve. According to the obtained averaged DSC curve, the melting of deprotonated DPPS lipids in LUVs occurs in an extremely wide temperature interval (50–59 °C, Table 1 ) [ 64 ] (for more details see Supplementary Materials, Figure S5 ), which is expected for systems in which the lipid domains subject to cooperative motion are significantly smaller [ 65 , 66 ], whereas the melting of protonated DPPS lipids (COOH) occurs in a temperature interval slightly wider than that of MLV ( T m, H ≈ 59–61 °C in LUV contrast to ≈60 °C in MLV, Table 1 )).…”