Self-assembled Instructive Extracellular Mimics

Abstract: One of the main challenges in modern medicine is the restoration of damaged or ageing tissues and organs. This is the realm of tissue engineering and more broadly that of synthetic regenerative biology. Main technical issues focus on how to stimulate or instruct individual cells to develop into a specific healthy tissue. Stem cells or progenitor cells that can differentiate into any tissue appear to provide an efficient solution to the biology of tissue repair. However, questions remain regarding physicochemical aspects of differentiation, in particular, the precise role of self-assembled extracellular matrices (ECM) and their cell-instructing interactions. Over the past years, a clear shift in the use of ‘passive materials’ to ‘instructive materials’ has been seen. Biomolecular self-assembly is an efficient strategy for biomaterial construction which can be programmed to support desired function. Self-assembling of peptides results in materials which represent a unique set of building blocks that form complex structures similar to ECM molecules. These highly modular systems can be designed to incorporate multiple biochemical signals and complex geometries.

Self- assembled peptide topology, which adopts a helical type of folding, enables the assembly of fibrous matrices, microscopic and biologically differential. These types of matrices are synthetic approximation of the native extracellular matrices, which shares key physico-chemical characteristics of the native systems including nanoscale order, hyper branched and knotted morphology and high persistence length of fibrillar structures. All these properties contribute to the formation of intricate fibrous networks that span nano-to-sub-millimeter dimensions thereby allowing for the continuous expression of unique bio-functional characteristics programmed in the sequence whose biological performance, scaffold support for mammalian cell proliferation and resistance against bacterial colonization, correlates with their morphological and chemical properties promoting thus an architectural model for differential extracellular matrices1,2.

 

1Differentially instructive extracellular protein micro-nets, J Am Chem Soc, 136, 7889-7898 (2014).

2Exploitable length correlations in peptide nanofibres, Nanoscale, 6, 11425-11430 (2014).

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