How does collagen adsorb on hydroxyapatite? Insights from ab initio simulations on a polyproline type II model

Bone has a hierarchical structure based on the mineralized fibril, an organic matrix envisaging collagen protein in tight interaction with hydroxyapatite mineral (HAP) and stabilized by water molecules. The tremendous complexity of this natural composite material hides the extraordinary features in terms of high compressive strength and elasticity imparted by the collagen protein. Clearly, understanding the nanoscale interface and mechanics of bone at atomistic level can dramatically improve the development of biocomposite and the understanding of bone related diseases. In this work, we aim at elucidating the features of the interaction between a model of a single-collagen-strand (COL) with the most common dried P-rich (010) HAP surface. The methods of choice are static and dynamic simulations based on density functional theory at PBE-D2, PBE-D3 and B3LYP-D3 levels. Collagen is made to a large extent by proline (PRO) and derivatives, and PRO’s side chain is known to affect the collagen triple helix stability dramatically. However, the role of the PRO side chain in the COL/HAP interface has never been studied so far at a quantum mechanical level. To decrease the enormous structural complexity of collagen itself, we employed a simple collagen model, i.e., a single strand based on the poly-L-proline type II polymer (PPII), which, for its composition, nicely suites our purposes. We discovered that during the HAP adsorption process, the polymer deforms to create a relatively strong electrostatic interaction between the PRO carbonyl CO group and the most exposed Ca ion of the P-rich (010) HAP surface. Both dynamic and static simulations agree that the HAP surface guides the formation of PPII conformers, which would be unstable without the support of the HAP surface. The PROs puckering and the polymer orientation affect the PPII affinity for the HAP surface with binding energies spanning within the 63−126 kJ·mol−1 range. This work is the first step toward the development of a full collagen model envisaging a three- interlocked helical polymer interacting with the HAP surfaces.