ERC Story - Sponge enzymes: nature’s little bio-builders
Biomineralisation is the formation of composite structures containing inorganic materials by living organisms – for example, an eggshell or a tooth. Biosilica is an important biomineral – produced on the scale of gigatons through biosilification, mainly by marine organisms, such as siliceous sponges. The delicate, intricate biosilica structures found in siliceous sponges measure from nanometres to millimetres in length. These beautiful open frameworks of rod and star-shaped biosilica spicules have amazed scientists since they were first observed. But to the more application-oriented eye, they have other interesting features: nanometre-scale silica structures form vital components in micro- and nanoelectronics, such as insulators and optical wave guides. In addition, biosilica holds the promise of biocompatibility – a vital property for medical implants. At the University Medical Center of Johannes Gutenberg University Mainz in Germany, Professor Werner E. G. Müller and his co-workers in the Institute for Physiological Chemistry are using an ERC Advanced Grant to uncover the fundamental mechanisms of biomineralisation, in particular biosilicification, and to harness its processes for a range of exciting new technologies. "The beauty of nature is that it finds strategies to make things happened. In chemistry, change is constrained by the activation energy needed for a chemical reaction – you must put in a lot of energy in order to get things going," says Werner Müller, "In contrast, biochemical reactions get round this through using natural catalysts to reduce the activation energy required. In biosilicification, it is enzymes that play this catalytic role." Indeed, he points out, fabricating silica nanostructures and optical components at present involve extreme conditions: temperatures of around 1000ºC for silica optical fibres. Yet sponges achieve similar results at ambient temperatures and with much less energy expenditure by using enzymes that expedite chemical processes simply by binding transiently to the materials involved. Building on a new paradigm "The discovery of the enzyme catalyst silicatein in the last decade, and its role in the formation of inorganic biosilica, produced a paradigm change for researchers. We now know that only a few enzymes can control reactions, but our research shows that it is not limited to biosilica – other biomaterials containing metals can also be produced using specific enzymes,” explains Professor Müller. His team is taking biosilicification research further by bringing in cutting-edge techniques from structural biology, biochemistry, bioengineering and material sciences. Already this research has borne fruit in a parallel Si-Bone Proof-of-Concept (PoC) awarded by the ERC. "Sponge structures are extremely diverse and it’s the same for animal bones; each species has its own specific body plan. Even though we don’t know how this is determined in humans, we have discovered that bone growth is controlled by enzymes as well, which led us to produce prosthetic implants using biosilica made in vitro. These implants have been proved highly biocompatible in animal experiments – they are not rejected by the host organism" "We are also discovering that they offer other benefits: they are biodegradable over time, thus removing the need for surgery to remove them, as it is done for metal pins for repairing fractures. Even better, this slow biodegradation allows for a controlled regrowth of new bone, indeed the biosilica also seems to promote new bone growth. This is not so surprising since human bodies contain biosilica and glassy sponges were among the first organisms to evolve on earth. They are thought to be the ancestors of vertebrates – so a strong biocompatibility reflects this. "In Si-Bone-PoC, we are taking this research forward. In particular, we are looking at the role which the silicatein enzyme might play in preventing and even curing osteoporosis, an age-related bone disease that brings huge costs and great misery to sufferers, and which is on the rise as we live longer." - Source: Professor Werner Ernst Ludwig Georg Müller - Project coordinator: University Medical Center of Johannes Gutenberg University Mainz, Germany - Project title: From gene to biomineral: Biosynthesis and application of sponge biosilica - Project acronym: BIOSILICA - Institution website - FP7 funding programme (ERC call): Advanced Grant 2011 - EC funding: EUR 2 200 000 - Project duration: 5 years references müller W.E.G. Wang X.H. Grebenjuk V., Diehl-Seifert B., Steffen R., Schloßmacher U., Trautwein A., Neumann S. and Schröder H.C. (2013), Silica as a morphogenetically active inorganic polymer: effect on the BMP-2-dependent and RUNX2-independent pathway in osteoblast-like SaOS-2 cells; Biomaterials Sci. 1: 669-678 müller W.E.G. Schröder H.C. Burghard Z., Pisignano D. and Wang X.H. (2013), Silicateins – A novel paradigm in bioinorganic chemistry: Enzymatic synthesis of inorganic polymeric silica; Chemistry Eur. J., 19:5790-5804 wang, X.H. Schröder, H.C. Wang, K., Kaandorp, J.A. and Müller, W.E.G. (2012), Genetic, biological and structural hierarchies during sponge spicule formation: From soft sol-gels to solid 3D silica composite structures; Soft Matter, 8:9501-9518.