Biological mineralized tissues are sophisticated organic-inorganic composites that are assembled bottom-up. They exhibit a highly hierarchical architecture with characteristic length scales that span many orders of magnitude. Functional roles include mechanical support, feeding, locomotion, defense, and sensing of light, gravity, and the magnetic field. Highly evolved design enables features such as high bone toughness at low weight, self-sharpening teeth, and continuous adaptive remodeling/self-repair. Biosynthesis typically occurs near ambient conditions in aqueous environments, using abundantly available building blocks. Such mild conditions have a low carbon footprint and are environmentally sustainable. Despite these highly attractive properties and great progress in bio-inspired material synthesis, many of the hallmarks of biological crystal growth have yet to be reproduced in vitro: polymorph control, shaping of non-faceted, curving and/or branching single crystals, and nm scale control of organic-inorganic composites. Clearly, much could be gained by developing a biotechnological alternative to bulk materials synthesis. Building on the work of Okazaki, Wilt, and others, we have established a unique system in which we can control in vitro crystal growth, inside cooperating cells, and using external and internal guidance cues. In particular, we are able to direct primary mesenchyme cells (PMCs) isolated from the sea urchin embryo to a) collaboratively deposit oriented calcite single crystals with smooth surfaces in specific locations using surface micro-patterning (Fig. 1.1A) and b) induce branching of single crystals along controlled crystallographic directions using a recombinant growth factor (rVEGF, Fig. 1.1B-E). We have thus achieved an unprecedented level of control over crystal growth by PMC. Our unique experimental system provides a basis for investigating fundamental biological mechanisms that cannot be probed in vivo (VEGF concentration cannot be controlled) and offers an innovative approach to genetically engineered materials – building on and expanding a materials genome in the literal sense of the word. Herein, we propose to investigate how PMCs control crystal growth at three length scales. At the atomic scale, we will focus on mineral-protein interactions. At the subcellular level, we will investigate the role of the cytoskeleton. Finally, we aim to connect systems level processes, namely amplitude and timing of rVEGF pulses, to changes in the protein makeup and mineral/matrix interactions. We thus address the challenges in hard materials and composites identified in the Report on the 2012 NSF Biomaterials Workshop. Taken together, the anticipated results will a) provide a mechanistic basis for bio-inspired approaches to controlling crystal growth and b) enable rational bioengineering of the spicule deposition process in PMC cultures. The proposed research will impact the development of sustainable solutions materials synthesis and contribute to incorporating the biological with the anthropogenic materials genome. It is conceivable to scale up the process described in the proposal to large-scale biological fixation of the greenhouse gas CO2 and, in this manner, support the battle against global warming. In addition, the unraveling of the mechanism of the biosynthetic machinery will feed back into the field of cell and developmental biology. At last, but not at least, an important component of the proposed activity is an education and outreach-plan that complements the research objectives and is well
|Effective start/end date||1/1/20 → 12/31/22|
- National Science Foundation (DMR-1905982-002)
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