Two-Dimensional Self-Assembly of Collagen-Mimetic Peptides Open Access

Jiang, Tao (2015)

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Peptide self-assembly has intrigued researchers for decades, as it offers a practical way for fabrication of biomaterials with defined structure and function. Challenge and opportunity still exist in this field where de novo peptide design cannot afford structures as sophisticated as natural ones in cells. This dissertation described the effort we have made in controlling self-assembly on scaffold of collagen-mimetic peptides.We first demonstrated the design of two collagen-mimetic peptides, NSI and NSII comprising three sequential blocks with positive, neutral, and negative charges. Both peptides self-assembled into structurally defined sheets. Characterizations suggested a self-assembly mechanism that the triblock configuration enforced an anti-parallel alignment of collagen triple helices through complementary electrostatic interactions. Lateral extension and layered packing of triple helices afforded the two-dimensional assembly formation. A clear understanding of the underlying structures provided an attractive platform for fabrication of two-dimensional structures by mediating electrostatic interactions. We then investigated the effects of positions and conformations of charged residues on self-assembly morphology. NSIII was described in this chapter, which self-assembled into monolayer sheets of uniform size and shape. It was proposed that the sequence change in NSIII introduced an energy penalty against Coulombic attraction energy among triple helices. The assembly force was balanced by the disassociation force, which resulted in the formation of small and uniform assemblies. Finally, we presented a rational peptide design on the basis of the previous sheet model. Two asymmetric peptides, CP+ and CP- were described that could form monolayer sheets with positive and negative surface charge, respectively. We took advantage of the difference in rates of assembly between CP+ and CP-, and grew CP- layers on faces of CP+ sheets with the aid of electrostatic interactions. Using this strategy, we generated an ordered sandwich structure, with CP+ sheet as core, buried by CP- layers. The results suggested an exciting possibility of building complex structures with compositional and structural control.

Table of Contents

1 Introduction 1

1.1 Self-assembly in nature 1

1.2 Molecular self-assembly using nature-inspired building blocks 2

1.3 Collagen-mimetic peptides 4

1.4 Supramolecular assembly of collagen-mimetic peptides 6

1.5 Summary 16

1.6 Reference 17

2 Structurally defined nano-scale sheets from self-assembly of collagen-mimetic peptides 21

2.1 Introduction 21

2.2 Collagen nanosheet sequences design 23

2.3 Results and discussion 25

2.3.1 Circular dichroism 25

2.3.2 Flow linear dichroism 28

2.3.3 Transmission Electron Microscopy 30

2.3.4 Atomic force microscopy 34

2.3.5 Solution X-ray scattering measurements 37

2.3.6 Electron diffraction measurements 39

2.3.7 Scanning transmission electron microscopy 42

2.3.8 Gold nanoparticle binding assay 45

2.3.9 Chemical modification of sheet surface 47

2.4 Summary 51

2.5 Materials and methods 54

2.6 Reference 65

3 Structurally homogeneous nanosheets from self-assembly of a collagen-mimetic peptide 71

3.1 Introduction 71

3.2 Nanosheet sequence design 72

3.3 Results and discussion 73

3.3.1 Circular dichroism 73

3.3.2 Transmission Electron Microscopy 75

3.3.3 Atomic force microscopy 77

3.3.4 Dynamic light scattering measurements 79

3.3.5 Solution X-ray scattering and electron diffraction measurements 81

3.3.6 Energy frustration mechanism 85

3.4 Summary 88

3.5 Materials and methods 89

3.6 Reference 94

4 Rational design of multilayer collagen nanosheets with compositional and structural control 97

4.1 Introduction 97

4.2 Asymmetric peptides design 99

4.3 Results and discussion 102

4.3.1 Circular dichroism 102

4.3.2 Transmission Electron Microscopy 105

4.3.3 Atomic force microscopy 111

4.3.4 Triple layer formation 113

4.3.5 Zeta potential measurements 117

4.3.6 Gold nanoparticle binding assay 120

4.3.7 Electrostatic force microscopy 123

4.3.8 Solution X-ray scattering measurement 125

4.3.9 Electron diffraction measurements 132

4.4 Summary 137

4.5 Materials and methods 140

4.6 Reference 148

5 Conclusion and outlook 155

5.1 Conclusion 155

5.2 Future directions 156

5.3 Reference 157

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