Design of nanostructured biological materials through self-assembly of peptides and proteins

Self Cite

761

490

Nanotechnology is often associated with materials fabrication, microelectronics, and microfluidics. Until now, the use of nanotechnology and molecular self assembly in biomedicine to repair injured brain structures has not been explored. To achieve axonal regeneration after injury in the CNS, several formidable barriers must be overcome, such as scar tissue formation after tissue injury, gaps in nervous tissue formed during phagocytosis of dying cells after injury, and the failure of many adult neurons to initiate axonal extension. Using the mammalian visual system as a model, we report that a designed self-assembling peptide nanofiber scaffold creates a permissive environment for axons not only to regenerate through the site of an acute injury but also to knit the brain tissue together. In experiments using a severed optic tract in the hamster, we show that regenerated axons reconnect to target tissues with sufficient density to promote functional return of vision, as evidenced by visually elicited orienting behavior. The peptide nanofiber scaffold not only represents a previously undiscovered nanobiomedical technology for tissue repair and restoration but also raises the possibility of effective treatment of CNS and other tissue or organ trauma.

Section: Self-assembling Peptide Nanofiber Scaffold (Sapns)mentioning

confidence: 91%

Section: Self-assembling Peptide Nanofiber Scaffold (Sapns)mentioning

confidence: 99%

Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

Ellis-Behnke

Liang

You

et al. 2006

Self Cite

761

490

“…On exposure to physiological osmolarity and pH, the peptides rapidly assemble into small nanofibers (Ϸ10 nm) that can be injected into the myocardium to form 3D cellular microenvironments (11,12). These peptide nanofiber microenvironments recruit a variety of cells including vascular cells (12).…”

mentioning

confidence: 99%

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

Davis

Hsieh²,

Takahashi³

et al. 2006

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563

411

Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a ''biotin sandwich'' approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy.engineering ͉ maturation ͉ scaffold

“…These natural systems offer inspiration in the effort to engineer novel assemblies through de novo design. Such studies are in their infancy, but interest in the area is intense because an ability to engineer or design water-soluble self-assembling systems offers routes to novel biomaterials with potential applications in synthetic biology and nanobiotechnology (2)(3)(4)(5)(6)(7)(8), for instance, the preparation of biocompatible scaffolds for regenerative biology (cell and tissue engineering) (9).…”

mentioning

confidence: 99%

Engineering nanoscale order into a designed protein fiber

Papapostolou

Smith

Atkins

et al. 2007

238

250

We have established a designed system comprising two peptides that coassemble to form long, thickened protein fibers in water. This system can be rationally engineered to alter fiber assembly, stability, and morphology. Here, we show that rational mutations to our original peptide designs lead to structures with a remarkable level of order on the nanoscale that mimics certain natural fibrous assemblies. In the engineered system, the peptides assemble into two-stranded ␣-helical coiled-coil rods, which pack in axial register in a 3D hexagonal lattice of size 1.824 nm, and with a periodicity of 4.2 nm along the fiber axis. This model is supported by both electron microscopy and x-ray diffraction. Specifically, the fibers display surface striations separated by nanoscale distances that precisely match the 4.2-nm length expected for peptides configured as ␣-helices as designed. These patterns extend unbroken across the widths (>50 nm) and lengths (>10 m) of the fibers. Furthermore, the spacing of the striations can be altered predictably by changing the length of the peptides. These features reflect a high level of internal order within the fibers introduced by the peptidedesign process. To our knowledge, this exceptional order, and its persistence along and across the fibers, is unique in a biomimetic system. This work represents a step toward rational bottom-up assembly of nanostructured fibrous biomaterials for potential applications in synthetic biology and nanobiotechnology.bionanoscience ͉ nanofibers ͉ peptide assembly ͉ rational protein design ͉ self-assembly