Utilizing DNA Nanotechnology to Unveil the Effects of Receptor Forces on Cell Maturation and Function Restricted; Files Only

Abstract

This dissertation examines the fundamental biological processes of cell differentiation and maturation, which are mediated by piconewton forces that cells transmit to their receptors. However, the challenge of substrate dependency in the cell-generated forces poses a significant obstacle to studying and understanding these processes. This study utilizes a range of innovative DNA-based tension-sensing techniques to measure and modulate receptor forces to address this issue. This approach provides new insights into the impact of molecular forces and rigidity on complex phenomena, such as cardiac muscle maturation and stem cell differentiation. The dissertation is structured into five chapters, which explore topics such as cardiac mechanobiology, the development and expansion of DNA-based sensors, and a novel cell sorting technique based on mechanical phenotypes. Moreover, this study presents a hydrogel-based matrix that overcomes the limitations of non-physiologically relevant stiff substrates in the field of mechanotransduction. In summary, this dissertation represents a significant contribution to the scientific understanding of the mechanics of biological processes and holds great promise for future research in this field.

Table of Contents

TABLE OF CONTENTS

List of abbreviations

CHAPTER 1. INTRODUCTION

1.1 Cardiomyocyte mechanotransduction

1.2 Stem cell mechanics and tissue regeneration

1.3 Different techniques to measure and manipulate cellular forces

1.4 Mechanotagging and its importance

1.5 Aim and scope of this dissertation

References

CHAPTER 2. DNA tension sensors show cardiac muscle maturation is sensitive to pN receptor force 

2.1 Abstract

2.2 Introduction

2.3 Results and discussions

2.4 Conclusions

2.5 Materials and methods

2.6 Appendix

Reference

CHAPTER 3. Mechanically sorting cells using TaCT probes

3.1 Abstract

3.2 Introduction

3.3 Results and discussions

3.4 Conclusions

3.5 Materials and methods

3.5 Appendix

Reference

CHAPTER 4. HYDROGEL-BASED CELLULAR TENSION-SENSING MATRIX

4.1 Abstract

4.2 Introduction

4.3 Results and discussions

4.4 Conclusions

4.5 Materials and methods

4.6 Appendix

Reference

CHAPTER 5. SUMMARY AND OUTLOOKS

5.1 Summary

5.2 Perspective

5.3 Other contributions

   5.4 Outlook

About this Dissertation

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School	Laney Graduate School
Department	Chemistry
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Chemistry, Biochemistry Biology, Molecular Biophysics, Biomechanics
Keyword	Mechanobiology Traction force microscopy Mechanotransduction Cell receptor forces
Committee Chair / Thesis Advisor	Khalid Salaita, Emory University
Committee Members	Yonggang Ke, Emory University Bill Wuest, Emory University

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