Abstract

Mineralo-organic nanoparticles form spontaneously in human body fluids when the concentrations of calcium and phosphate ions exceed saturation. We have shown previously that these mineralo-organic nanoparticles possess biomimetic properties and can reproduce the whole phenomenology of the so-called nanobacteria—mineralized entities initially described as the smallest microorganisms on earth. Here, we examine the possibility that various charged elements and ions may form mineral nanoparticles with similar properties in biological fluids. Remarkably, all the elements tested, including sodium, magnesium, aluminum, calcium, manganese, iron, cobalt, nickel, copper, zinc, strontium, and barium form mineralo-organic particles with bacteria-like morphologies and other complex shapes following precipitation with phosphate in body fluids. Upon formation, these mineralo-organic particles, which we term bions, invariably accumulate carbonate apatite during incubation in biological fluids; yet, the particles also incorporate additional elements and thus reflect the ionic milieu in which they form. Bions initially harbor an amorphous mineral phase that gradually converts to crystals in culture. Our results show that serum produces a dual inhibition-seeding effect on bion formation. Using a comprehensive proteomic analysis, we identify a wide range of proteins that bind to these mineral particles during incubation in medium containing serum. The two main binding proteins identified, albumin and fetuin-A, act as both inhibitors and seeders of bions in culture. Notably, bions possess several biomimetic properties, including the possibility to increase in size and number and to be sub-cultured in fresh culture medium. Based on these results, we propose that bions represent biological, mineralo-organic particles that may form in the body under both physiological and pathological homeostasis conditions. These mineralo-organic particles may be part of a physiological cycle that regulates the function, transport and disposal of elements and minerals in the human body.

Highlights

  • Mineralo-organic complexes in the form of amorphous and crystalline nanoparticles (NPs) have been observed in various body fluids [1,2,3,4,5,6,7,8,9,10]

  • While our studies have disproved the NB hypothesis, it is clear that the NPs formed by minerals and organic compounds are no less real, and they have been documented in all the body fluids that we have studied to date, including serum [2,3,6,10] and a number of other body fluids [2,7]

  • In the context of human physiology, the fact that bions spontaneously precipitate from elements and ions that are ubiquitous in biological fluids (e.g., Ca2+, PO43, Na+, Mg2+, Mn2+) suggests that the mineralo-organic particles may form in the human body

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Summary

Introduction

Mineralo-organic complexes in the form of amorphous and crystalline nanoparticles (NPs) have been observed in various body fluids [1,2,3,4,5,6,7,8,9,10]. The prevalent forms of minerals that aggregate with organics (proteins, peptides, amino acids, lipids, carbohydrates, and so forth) have been shown to contain predominantly carbonate hydroxyapatite (HAP) structures, which show a tendency to aggregate and to undergo phase transformation In the process, they assume marked morphological pleomorphism, with the spherical NPs flattening out to become spindles, platelets, and films [1,2,3,4,5,6,7,8,9,10]. NB-like forms can be replicated in vitro by using purified proteins and ions [4]

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