Synthetic extracellular matrices with function-encoding peptides

Abstract

The communication of cells with their surroundings is mostly encoded in the epitopes of structural and signalling proteins present in the extracellular matrix (ECM). These peptide epitopes can be incorporated in biomaterials to serve as function-encoding molecules to modulate cell-cell and cell-ECM interactions. In this Review, we discuss natural and synthetic peptide epitopes as molecular tools to bioengineer bioactive hydrogel materials. We present a library of functional peptide sequences that selectively communicate with cells and the ECM to coordinate biological processes, including epitopes that directly signal to cells, that bind ECM components that subsequently signal to cells, and that regulate ECM turnover. We highlight how these epitopes can be incorporated in different biomaterials as individual or multiple signals, working synergistically or additively. This molecular toolbox can be applied in the design of biomaterials aimed at regulating or controlling cellular and tissue function, repair and regeneration.

Keywords: Bioinspired materials.

Fig. 1. Function-encoding peptide epitopes.

a, Classification  and examples of peptide epitopes. b, Synthetic hydrogels endowed with function-encoding epitopes can induce multiple biological effects, such as adhesion, differentiation, immunomodulation and matrix turnover in encapsulated cells. ECM, extracellular matrix; MMP, matrix metalloproteinase.

Fig. 2. Peptide epitopes in synthetic hydrogels for direct signalling.

a,b, Peptide epitopes inducing direct signalling include: (a) adhesion peptides operating, for example, through integrin binding, and (b) growth factor-mimetic peptides mimicking, for example, transforming growth factor-β (TGFβ) molecules that bind to TGFβ receptors (TGFβR). c,d, Other peptides have been explored for immunomodulatory effects, including (c) antimicrobial peptides able to disrupt bacteria cell membranes and (d) immunomodulatory peptides that elicit immune-cell responses. MHC, major histocompatibility complex; Smad, small mothers against decapentaplegic protein.

Fig. 3. Peptide epitopes in synthetic hydrogels that bind to extracellular matrix components.

a–c, Peptide sequences that can bind extracellular matrix (ECM) components to allow matrix degradation include epitopes that bind (a) growth factors, (b) ECM components and (c) ions. d, Enzymatically cleavable peptides can be exploited to create dynamic matrices. MMP, matrix metalloproteinase.