Mimetic models of matrix vesicles to study the action of sphingomyelinase

• Grant number: 23/01644-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Pietro Ciancaglini
• Grantee: Juliana do Rosário Silva de Sousa
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization, AP.TEM

Abstract

Mineralization of bone tissue is a highly ordered process that begins with the release of matrix vesicles (MVs) from the plasma membrane of osteogenic cells, which are responsible for providing the necessary conditions for the nucleation and growth of the first calcium phosphate minerals, which are subsequently released into the organic matrix of the bone for the continuation of the process. Little is known about the factors that regulate the sprouting of MVs from progenitor cells, however, the presence of Sphingomyelinase (nSMase2), a key enzyme in the biogenesis of extracellular vesicles and also present in the proteome of MVs, allows some speculations. In this context, this IC project proposes a comprehensive study of the interaction of nSMase2 with membrane models (lipossomes) that mimic the lipid composition of MVs (abundant in cholesterol and sphingomyelin). Interactions in bilayer models will be evaluated using classical nanoparticle characterization techniques (DLS, NTA, AFM, zeta potential), in addition to calorimetric analysis. The results generated by the project (which are in synergy with Thematic Project 2019/08568-2) could open new paths for the elucidation and control of the biogenic pathway of MVs, essential for a better understanding of the bone formation process, as well as for the development of therapeutic approaches for more efficient bone regeneration/repair.