Modular self-assembling biomaterials for directing cellular responses

Abstract

Self-assembling biomaterials are promising as cell-interactive matrices because they can be constructed in a modular fashion, which enables the independent and simultaneous tuning of several of their physicochemical and biological properties. Such modularity facilitates the optimization of multi-component matrices for use in complex biological environments such as 3-D cell culture or scaffolds for regenerative medicine. This Highlight will discuss recent strategies for producing modular self-assembling biomaterials, with a particular focus on how ligand presentation and matrix mechanics can be controlled in modular ways. In addition, it will discuss key hurdles that remain for employing these materials as cell-interactive scaffolds in biomedical applications, particularly those that relate to how they may interface with the immune system.

A self-assembling peptide acting as an immune adjuvant

“…However, similar to Q11 and to other previously reported Q11 derivatives (16,17,22,23), it formed networks of laterally entangled fibrils when it was first dissolved in water and then added to salt-containing buffers such as phosphate-buffered saline (PBS), (Fig. 1A, Fig.…”

“…One strategy that has received attention recently is based on fibrillized peptides, peptidomimetics, and peptide derivatives, which are being explored for a variety of biomedical and biotechnological applications, most notably as scaffolds for regenerative medicine (18,19) and defined matrices for cell culture (20,21). In these applications, selfassembled materials provide several advantages, including multifunctionality, multivalency, synthetic definition, molecular specificity, and control over the nanoscale positioning of ligands and other biomolecular features (17). In our laboratory, we have previously developed self-assembled, multicomponent matrices for cell culture using a short fibrillizing peptide, Q11 (Ac-QQKFQFQFEQQ-Am) (16,17,22,23).…”

“…To accomplish this, supramolecular self-assembly is rapidly becoming a synthetic method of choice (15)(16)(17). One strategy that has received attention recently is based on fibrillized peptides, peptidomimetics, and peptide derivatives, which are being explored for a variety of biomedical and biotechnological applications, most notably as scaffolds for regenerative medicine (18,19) and defined matrices for cell culture (20,21).…”

“…In these applications, selfassembled materials provide several advantages, including multifunctionality, multivalency, synthetic definition, molecular specificity, and control over the nanoscale positioning of ligands and other biomolecular features (17). In our laboratory, we have previously developed self-assembled, multicomponent matrices for cell culture using a short fibrillizing peptide, Q11 (Ac-QQKFQFQFEQQ-Am) (16,17,22,23). This peptide, like other previously reported short fibrillizing peptides (21, 24-26), β-hairpins (27), peptide-amphiphiles (19, 28), and peptide derivatives (29), self-assembles in salt-containing aqueous environments to form networks of β-sheet-rich nanofibers.…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…In addition, differently charged peptide helices, which can build a coiled coil, can be used for a directed presentation of molecules for several biochemical applications (Reinhardt et al, 2014;Lequoy et al, 2016). An advantage of peptide self-assembly strategies is the generation of highly modular fibrils that can additionally create a structural ECM-mimetic to support cell adhesion (Collier, 2008;Jung et al, 2011;Ceylan et al, 2012). Functional molecules can be also combined by the high affinity between biotin and streptavidin (avidin) ( Figure 4C) (Freitas et al, 2012;Gorbahn et al, 2012).…”