Mechanical Unfolding Response of Proteins
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Mechanical Unfolding Response of Proteins

Author(s):
Publication Date:
June 16, 2023
Copyright © 2023 American Chemical Society
eISBN:
‍9780841299740
DOI:
10.1021/acsinfocus.7e7015
Read Time:
five to six hours
Collection:
2
Publisher:
American Chemical Society
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Mechanical Unfolding Response of Proteins is a thermodynamically motivated overview of when, why, and how proteins respond to mechanical perturbations and the experimental techniques used to probe single protein biophysics. Relative newcomers to the field (new graduate students), and those starting from a biological background hoping for an introduction to the physics behind protein behavior, will benefit from reading this primer.

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Detailed Table of Contents
About the Series
Preface
Chapter 1
Protein Folding and Structure
1.1
Introduction
1.2
Protein Structure
1.2.1
Primary Structure of Proteins
1.2.2
Secondary Structure of Proteins
1.2.3
Tertiary Structure of Proteins
1.2.4
Quaternary Structure of Proteins
1.3
The Main Stages of Protein Folding
1.3.1
The Ribosome and How the Polypeptide Chain Is Assembled
1.3.2
The Entropic Collapse Reduces the Conformational Space of a Polypeptide Chain
1.3.3
The Hydrophobic Collapse and the Molten Globule Structures
1.3.4
The Native State of Proteins
1.3.5
Timing and Energy Landscape Representation of the Folding Process
1.4
Proteins and Polyproteins
1.5
Chemical, Thermal, and Mechanical Stabilities
1.5.1
Chemical Denaturation
1.5.2
Temperature and Thermal Stability
1.5.3
Force and Mechanical Perturbations
1.6
That’s a Wrap
1.7
Read These Next
Chapter 2
Energy Landscapes as the Protein’s Blueprint
2.1
What Is an Energy Landscape?
2.2
Two-State Model of Protein Folding/Unfolding
2.3
Proteins and Polymers
2.4
Multidimensionality
2.5
That’s a Wrap
2.6
Read These Next
Chapter 3
Protein Functioning under Force
3.1
Introduction: Proteins and Mechanical Forces
3.2
Unfolding under Force
3.3
Refolding against Force
3.4
Regulating Mechanical Stresses to Proteins Unfolding/Refolding
3.5
That’s a Wrap
3.6
Read These Next
Chapter 4
Methods to Study the Mechanical Unfolding of Proteins
4.1
Introduction
4.2
In Vitro Force Spectroscopy Methods
4.2.1
Attachment Chemistries for Single Molecule Force Spectroscopy Methods
4.2.1.1
Nonspecific Physical Interactions
4.2.1.2
Specific Noncovalent Interactions
4.2.1.3
Specific Covalent Interactions
4.2.2
Single Molecule Force Spectroscopy Methods
4.2.2.1
Magnetic Tweezers (MT)
4.2.2.2
Atomic Force Microscopy (AFM)
4.2.2.3
Optical Tweezers (OT)
4.3
In Vivo and Tissue-like Approaches to Study Protein Unfolding
4.3.1
Molecular Tension Probes
4.3.2
Protein Hydrogels and Tissue-like Materials
4.4
In Silico Methods: Steered Molecular Dynamics (MD) Simulations
4.5
Concluding Remarks on Limitations of the Measuring Techniques to Study Mechanical Response of Proteins
4.6
That’s a Wrap
4.7
Read These Next
Chapter 5
How Cells and Tissues Use Mechanical Unfolding and Refolding as a Gain-of-Function
5.1
Key Characteristics Related to Mechanical Unfolding and Refolding of Proteins In Vivo
5.1.1
Exposure of Buried Reactive Site
5.1.2
Energy Storage and Release
5.1.3
A Quantized Response
5.1.4
Fine-Tuned Unfolding Response through Ligand Binding
5.2
Muscular Contraction and Protein Refolding-Induced Function
5.3
Cellular Mechanotransduction Regulates Dynamics of the Cellular Cytoskeleton
5.4
How Cells in Our Ears Transform Pressure Waves into Perceived Sound
5.5
Force-Regulated Attachment of Bacterial Adhesion
5.6
Degradation of Proteins Requires Mechanical Unfolding of the Tertiary Structure
5.7
Concluding Remarks
5.8
That’s a Wrap
5.9
Read These Next
Bibliography
Glossary
Index
Reviewer quotes
Sarah Innes-Gold, Postdoctoral Fellow, Harvard University Department of Chemistry and Chemical Biology
My background is in polymer physics and SMFS, but I have limited knowledge of protein mechanics. I appreciated the discussion of proteins in the context of more familiar physical/energetic frameworks, especially when examples of specific proteins were given. The insights into the downstream biological signaling that mechanical changes can affect were particularly useful.
Author Info
Ionel Popa
Ionel Popa graduated with a Bachelor of Chemical Engineering in from Gh. Asachi Technical University, in Iasi, Romania, and obtained his doctoral degree in Chemistry and Biochemistry from University of Geneva, in Switzerland, while working with Prof. Michal Borkovec. He then joined the Department of Biological Sciences at Columbia University, first as a postdoc and later as an associate research scientist. At Columbia he worked with Prof. Julio M. Fernandez, where they developed a novel approach based on magnetic tweezers and covalent attachment that can study the mechanical unfolding of a single protein molecule for many hours or days. Since 2015, he joined the Physics Department at the University of Wisconsin-Milwaukee, where he runs the Laboratory for Advanced Biopolymers and Nanomechanics of Proteins (ALBNanoPro). He is studying how the mechano-biology of proteins relate to how our muscles work, how cancer develops and spreads, and how bacteria adhere and interact with antibodies.
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Ronen Berkovich
Ronen Berkovich received his B.Sc. in Chemical Engineering from Technion in 2002, and after pursuing several years in the industry as an engineer, he obtained his Ph.D. from the Department of Chemical Physics at Tel-Aviv University in 2010 in Chemical Physics with Prof. Joseph (Yossi) Klafter and Prof. Michael Urbakh. He completed postdoctoral training at Columbia University at the Department of Biological Sciences with Prof. Julio M. Fernandez, prior to joining the Department of Chemical Engineering at Ben-Gurion University of the Negev (BGU) as a faculty member in October 2013. Beyond single molecule biophysics, his research group is studying non-linear phenomena related to soft matter mechanics, nanotribology, and particle resuspension.
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