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

Author(s)

de Araujo Pimenta, Luciana ^{[1, 2]} ; Duarte, Evandro L. ^[3] ; Muniz, Gabriel S. Vignoli ^[3] ; Pasqualoto, Kerly Fernanda Mesquita ^[4] ; de Mattos Fontes, Marcos Roberto ^[5] ; Lamy, M. Teresa ^[3] ; Sampaio, Sandra Coccuzzo ^{[1, 2]}

Affiliation

^[1] Inst Butantan, Pathophysiol Lab, Av Vital Brazil 1500, BR-05503900 Butanta, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Lineu Prestes 1524, BR-05508900 Butanta, SP - Brazil

^[3] Univ Sao Paulo, Inst Phys, R Matao 1371, BR-05508090 Butanta, SP - Brazil

^[4] Alchemy Inovacao Pesquisa & Dev Ltda, Technol Based Business Incubator Sao Paulo IPEN U, Av Lineu Prestes 2242 Bldg D, BR-05508000 Butanta, SP - Brazil

^[5] Univ Estadual Paulista, Inst Biosci, Dept Biophys & Pharmacol, Prof Dr Antonio Celso Wagner Zanin 250, BR-18618689 Botucatu, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 DEC 9 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/11161-6 - Interaction Crotoxin and Macrophages: Study of the participation of Formyl Peptide Receptor and Lipid Domains in Mechanisms Involved in the Molecular Toxin-Membrane Recognition Process
• Grantee: Sandra Coccuzzo Sampaio Vessoni
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50983-3 - INCT 2014: complex fluids
• Grantee: Antonio Martins Figueiredo Neto
• Support Opportunities: Research Projects - Thematic Grants