Self-assemblies of electrostatically self-complementary peptides derived from different structural motifs Public

Abstract

Supramolecular self-assembly from peptides is a powerful bottom-up approach for the fabrication of bio-nanomaterials. Peptides are advantageous among the sequence-programmable oligomers because of their sequence-specificity and chemical diversity, hence offering a great opportunity to introduce functional complexity across length-scales. However, it is currently still challenging to achieve controlled fabrication of structurally and dimensionally defined assemblies. This dissertation presents our effort in the fabrication of one- and two-dimensional nanomaterials from the self-assemblies of peptide sequences that are electrostatically self-complementary. The general construct of the peptides consists of two end blocks with oppositely charged residues and a midblock that is neutral. The peptide sequences are designed based on two structural motifs, collagen triple helices and -sheets. The collagen-mimetic peptides (CMPs) fold into triple helices, which subsequently self-assemble into two-dimensional crystalline nanosheets via electrostatic interaction. In this work, we utilize CMPs for the construction of multicomponent nanosheets with tunable properties. Even though our study of the -strand mimetic peptides (BMPs) is still at its infancy, preliminary results indicate that the charge-complementary sequence design in combination with D-amino acid substitution promote very robust growth of BMPs into one-dimensional nanotubes. Our current findings suggest that the relatively simple design of electrostatically self-complementary peptides works across multiple structural motifs and may present a promising strategy for controlled fabrication of peptide-based nanomaterials.

Table of Contents

1. Chapter 1: A strategy for controlled fabrication of multicomponent two-dimensional nanosheets from collagen-mimetic peptides 1

       1.1.           Introduction 1

       1.2.           CMP candidates for mixed assemblies 8

       1.3.           Mixing and characterization of 4S(X)535 and 4S(X)545 nanosheets 11

                             1.3.1. Size distribution 12

                             1.3.2. Thermal stability 13

                             1.3.3. Fluorescent imaging 16

                             1.3.4. Additional thermal denaturation study to prove the successful mixing of the two peptides 18

                             1.3.5. Summary on the mixing of 4S(X)535 and 4S(X)545 peptides 20

       1.4.           Mixing and characterization of 4R(X)444 and 4S(Y)444 nanosheets 21

                             1.4.1. Size distribution 23

                             1.4.2. Thermal stability 25

                             1.4.3. Atomic force microscopy (AFM) height measurement 26

                             1.4.4. SAXS/WAXS scattering profiles 28

                             1.4.5. Summary on the mixing of 4R(X)444 and 4S(Y)444 peptides 31

       1.5.           Conclusion. 32

       1.6.           Experimental methods 33

       1.7.           References. 38

2. Chapter 2: Structurally and dimensionally defined multicomponent blended nanosheets from self-assembly of collagen-mimetic peptides     43

       2.1.           Introduction 43

       2.2.           Identifying a suitable temperature for incubating the mixed assemblies 45

       2.3.           Characterization of 4S(X)444 - 4S(X)454 blended nanosheets assembled at 15oC     

                             2.3.1. Size distribution 47

                             2.3.2. Thermal stability 49

                             2.3.3. AFM height measurement 50

                             2.3.4. Fluorescent imaging 50

                             2.3.5. SAXS/WAXS scattering profiles 52

                             2.3.6. High-resolution cryo-TEM analysis 53

       2.4.           Conclusion and outlook 60

       2.5.           Supplementary figures 61

       2.6.           Experimental methods 71

       2.7.           References 77

3. Chapter 3: Self-assemblies of homochiral and heterochiral b-strand mimetic peptides 78

       3.1.           Introduction 78

       3.2.           Different secondary structure conformations and assembly morphologies between K2F4E2 and K2(^DF)4E2        81

       3.3.           In-depth study on the assembly of K2(^DF)4E2 in water 85              

       3.4.           Discussion and future experiments 92   

                             3.4.1. Heterochirality promotes the self-assembly of BMPs 92

                             3.4.2. A mechanistic explanation for formation of nanotubes from K2(^DF)4E2 peptide 92

                             3.4.3. Future experiments 94

       3.5.           Supplementary figures 96

       3.6.           Experimental methods 98

      3.7.      References  101

About this Dissertation

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Laney Graduate School
Department	Chemistry
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biophysics, Biomechanics Chemistry, Biochemistry Chemistry, General
Mot-clé	Peptide self-assembly Bionanomaterials
Committee Chair / Thesis Advisor	Vincent Conticello, Emory University
Committee Members	David Lynn, Emory University Yonggang Ke, Emory University

Dernière modification

Primary PDF

Thumbnail	Title	Date Uploaded	Actions
	Self-assemblies of electrostatically self-complementary peptides derived from different structural motifs ()	2024-04-05 16:31:43 -0400	Press to Select an action Download

Supplemental Files

Thumbnail	Title	Date Uploaded	Actions