Phosphatidylserine controls calcium phosphate nucleation and growth on lipid monolayers: A physicochemical understanding of matrix vesicle-driven biomineralization

Author(s):Show less -

Cruz, Marcos A. E. ^[1] ; Ferreira, Claudio R. ^[1] ; Tovani, Camila B. ^[1] ; de Oliveira, Flavia A. ^[2] ; Bolean, Mayte ^[1] ; Caseli, Luciano ^[3] ; Mebarek, Saida ^[4] ; Millan, Jose Luis ^[2] ; Buchet, Rene ^[4] ; Bottini, Massimo ^{[2, 5]} ; Ciancaglini, Pietro ^[1] ; Ramos, Ana Paula ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Quim, FFCLRP, Fac Filosofia Ciencias & Letras Ribeirao Preto, Sao Paulo - Brazil

^[2] Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA 92037 - USA

^[3] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Sao Paulo - Brazil

^[4] Univ Lyon, UMR 5246, CNRS, ICBMS, Villeurbanne - France

^[5] Univ Roma Tor Vergata, Dept Expt Med, I-00133 Rome - Italy

• Document type: Journal article
• Source: Journal of Structural Biology; v. 212, n. 2 NOV 1 2020.
• Web of Science Citations: 0

Abstract

Bone biomineralization is an exquisite process by which a hierarchically organized mineral matrix is formed. Growing evidence has uncovered the involvement of one class of extracellular vesicles, named matrix vesicles (MVs), in the formation and delivery of the first mineral nuclei to direct collagen mineralization. MVs are released by mineralization-competent cells equipped with a specific biochemical machinery to initiate mineral formation. However, little is known about the mechanisms by which MVs can trigger this process. Here, we present a combination of in situ investigations and ex vivo analysis of MVs extracted from growing-femurs of chicken embryos to investigate the role played by phosphatidylserine (PS) in the formation of mineral nuclei. By using self-assembled Langmuir monolayers, we reconstructed the nucleation core - a PS-enriched motif thought to trigger mineral formation in the lumen of MVs. In situ infrared spectroscopy of Langmuir monolayers and ex situ analysis by transmission electron microscopy evidenced that mineralization was achieved in supersaturated solutions only when PS was present. PS nucleated amorphous calcium phosphate that converted into biomimetic apatite. By using monolayers containing lipids extracted from native MVs, mineral formation was also evidenced in a manner that resembles the artificial PS-enriched monolayers. PS-enrichment in lipid monolayers creates nanodomains for local increase of supersaturation, leading to the nucleation of ACP at the interface through a multistep process. We posited that PS-mediated nucleation could be a predominant mechanism to produce the very first mineral nuclei during MV-driven bone/cartilage biomineralization. (AU)

• FAPESP's process: 14/24249-0 - Association of osteogenic proteins in biominerals and metallic oxides doped with rare-earth: interaction with membrane models systems
• Grantee: Camila Bussola Tovani
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/08892-9 - Bioactive surfaces designed from Langmuir-Blodgett Films and Biominerals
• Grantee: Ana Paula Ramos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/20846-2 - Exploring the role of lipid-protein-mineral matrix on bone biomineralization: a biophysical approach using self-assembled films
• Grantee: Marcos Antonio Eufrásio Cruz
• Support Opportunities: Scholarships in Brazil - Doctorate