WEB Atomistic understanding of fibronectin adsorption on ceramic surfaces
Fibronectin (Fn) is a glycoprotein in the nanofibrous extracellular matrix, which plays a major role in mechanobiology and cell adhesion [Vogel2018]. To date, the ability of fibronectin to assemble into nanofibers in vivo is still not fully understood. We have recently introduced a new in vitro method to induce fibrillogenesis of fibronectin by extrusion through ceramic nanopores [Raoulfi2015]. To study the potential of ceramic surfaces to initiate fibrillogenesis of fibronectin in a cell-free environment, we here present our first in silico results on the interaction of individual Fn type III modules with Al2O3 and SiO2.
We used classical molecular dynamics simulations to study the adhesive properties of five individual Fn type III modules. In particular, the interactions of the highly flexible connectivity region and a newly introduced model for the Fn interchain domain with SiO2 and Al2O3 surfaces [Kulke2019, Buthenuth2012, Lid2017] were studied. The charge density of both ceramic surfaces was adjusted to physiological pH.
First, orientation - dependent adhesion forces on Al2O3 and SiO2 surface models were determined for all modules using the AMBER program package. Subsequently, the module orientations, which yielded maximum force peaks during interaction with the respective ceramic surfaces, were used as initial configuration for longer dynamic simulations with the GROMACS code to determine thermodynamically stable adsorption configurations.
Repulsive and attractive interactions were found for all modules, which depended on their orientation on the different ceramic surfaces. The resulting maximum interaction forces of some individual module orientations varied significantly between values from 0.3 nN to 1 nN per module for the different ceramic surfaces. We found the highest difference in interaction forces for the Fn interchain region with more than 1 nN on Al2O3 whereas SiO2 only yielded maximum interaction forces around 0.35 nN. Consequently, different fibronectin modules exhibited different preferred orientations on both ceramic surfaces. This finding indicates a varying accessibility of the RGD domain in 10 Fn III, which is important to understand integrin-mediated cell adhesion on ceramic surfaces.
In summary, our in silico results provide a basic understanding of material-driven fibrillogenesis of fibronectin in vitro and will enable us to tailor ceramic biomaterials to optimize cell adhesion.
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|Extended Abstract||Figure 1||The 10 Fn III module with the labelled cell adhesion sequence RGD on two different ceramic surfaces: Al2O3 (left) and SiO2 (right). The depicted orientations correspond to the configuration we obtained from the highest interaction forces. While 10 Fn III with a beta sheet lies flat on SiO2 and the RGD sequence points towards the underlying surface, the RGD sequence on Al2O3 is oriented at the top pointing directly into the solution phase.||2 MB||Download|