Introduction and Objectives

Engineering living tissues or organs critically depends on the use of scaffolds to attract, house and instruct host cells. To achieve this, the scaffolds need to be functionalised using different strategies. One of these strategies relies on the use designer peptides to decorate scaffolds. Peptide linkers have shown increasing importance in the production of bioactive materials for various biological applications. In particular, they act as natural linkers for merging multiple functional domains and for attaching active motifs on the surface to induce cells and to enhance the function of biomaterials. However, intense structural customization of the linkers is required prior to examine them under experimental conditions for challenging tissue engineering applications such as heart valve repair. Thus, we here apply computer-aided molecular design to construct the linkers including essential properties such as multiple motif presentations and binding on scaffolds/nanoparticles.

Materials and Methods

The 3D structures of known functional motif (collagen and fibronectin inducing) with linkers were used in the interactive molecular dynamics simulations, which were carried out under physiological conditions after parameterization of all atomic properties. The simulations are to solve Newton equation of motion for 100 nanoseconds at the parallel super computer using algorithms of Groningen machine for chemical simulations. The trajectories of the simulations were collected at regular interval for analysing molecular behaviours, molecular interactions and structural properties of the linkers.


Our recent modeling shows that the linkers based on valine and alanine can be used for merging dual bioactive motifs, which enhance the stimulation of collagen and fibronectin in human adipose derived stem cells under experimental conditions. By further applying the modeling strategy, here, we are developing linkers in specific conformations with surface attachment property. The computer aided-design used to analyse the structural role of key residues such as proline, serine, alanine, glycine, glutamic acid, lysine and cysteine in different lengths with several combinations to probe favourable linkers. The structural rigidity and self-assembly are the major molecular features that were used appropriately to create the efficient linkers for decoration and functionalization of biomaterials.


The design of customized linkers may offer many advantages for the production intelligent biomaterials with multi-functionality, enhanced bioactivity and to target specific sites/shapes for tissue engineering applications.


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