Collagen intrafibrillar mineralization as a result of the balance between osmotic equilibrium and electroneutrality

Abstract

Mineralisation of fibrillar collagen with biomimetic process-directing agents has enabled scientists to gain insight into the potential mechanisms involved in intrafibrillar mineralisation. Here, by using polycation- and polyanion-directed intrafibrillar mineralisation, we challenge the popular paradigm that electrostatic attraction is solely responsible for polyelectrolyte-directed intrafibrillar mineralisation. Because there is no difference when a polycationic or a polyanionic electrolyte is used to direct collagen mineralisation, we argue that additional types of long-range non-electrostatic interactions are responsible for intrafibrillar mineralisation. Molecular dynamics simulations of collagen structures in the presence of extrafibrillar polyelectrolytes show that the outward movement of ions and intrafibrillar water through the collagen surface occurs irrespective of the charges of polyelectrolytes, resulting in the experimentally verifiable contraction of the collagen structures. The need to balance electroneutrality and osmotic equilibrium simultaneously to establish Gibbs-Donnan equilibrium in a polyelectrolyte-directed mineralisation system establishes a new model for collagen intrafibrillar mineralisation that supplements existing collagen mineralisation mechanisms.

Contribution of Mitophagy to Cell‐Mediated Mineralization: Revisiting a 50‐Year‐Old Conundrum

“…Larger ACP granules were identified in the autolysosomes, probably because of the aggregation of fluidic ACP droplets derived from the degraded mitochondria. These droplets are liquid‐like and moldable prior to their transformation into crystalline CaP phases 1, 18. After their transfer to the extracellular milieu via exocytosis,3 the ACP droplets remained amorphous initially (Figure S2A, Supporting Information) and co‐existed with the unmineralized collagen fibrils (Figure S2B, Supporting Information).…”

“…Abnormality in this process results in highly morbid pathological conditions such as osteoporosis, osteoarthritis, osteogenesis imperfecta, or Paget's disease. Biomineralization is initiated via amorphous calcium phosphate (ACP) precursors that infiltrate the extracellular collagen matrix and subsequently transform into intrafibrillar carbonated apatite 1. The ACP precursor phase, in turn, is produced by coalescence of prenucleation clusters of hydrated calcium and phosphate ionic aggregates 2.…”

“…The ACP precursor phase, in turn, is produced by coalescence of prenucleation clusters of hydrated calcium and phosphate ionic aggregates 2. Although the mechanisms of intrafibrillar mineralization of collagen fibrils have been well established,1 the process by which ACP precursors are produced and transported to the extracellular mineralization sites has not been completely elaborated.…”

Amorphous Phase Mediated Crystallization: Fundamentals of Biomineralization

“…It was found that the presence of the highly charged polymer is vitally important to the successful oriented crystallization of apatite inside collagen fibrils. Charged polymers mimicking NMPs may make ACP precursors liquid-like (called polymer-induced liquid-like precursors, PILPs) [31] and highly-charged [110], or they may alter the osmotic pressure [111], which in the end facilitates ACP precursors to go inside collagen fibrils. Olstza et al reported that with the PILP process [31], ACP precursors can be infiltrated into collagen fibrils.…”

Biodegradable mesoporous delivery system for biomineralization precursors

“…Inspired by the effect of long-chain polyamines on stabilization of orthosilicic acid during biosilicification of silica-containing organisms, Niu et al have developed poly(allylamine)-stabilized ACP (PAH-ACP) for intrafibrillar mineralization of collagen. 32 However, it is not known whether this novel PILP phase remains effective for biomineralization following its loading, storage, and release from the pMSN. Accordingly, three hypotheses were tested in the present study: 1) positively charged PAH-ACP may be effectively loaded and released from nonfunctionalized pMSN; 2) PAH-ACP released from loaded pMSN still retains its ability to infiltrate and mineralize collagen fibrils; and 3) complete degradation of pMSN occurs following unloading of their PAH-ACP cargo.…”