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Molecular Force Sensors
Author(s):
Publication Date:
March 9, 2022
Copyright ©
2022 American Chemical Society
eISBN:
9780841299177
DOI:
10.1021/acsinfocus.7e4008
Read Time:
five to six hours
Collection:
1
Publisher:
American Chemical Society
Molecular force sensors are a powerful tool for studying the mechanics of cells. These sensors not only provide information on the general mechanical behavior of cells but also can help elucidate the mechanical markers of disease formation and progression. For example, can we use cell mechanics as a biomarker to diagnose cancer? What are the mechanics associated with immune system function? Can cell mechanics be used to better understand the effect of drug treatments?
The number of available questions in the field of mechanobiology is endless. After reading this e-book, you will be equipped with the information needed to begin designing your own molecular force sensors, and to begin answering the multitude of questions surrounding cell mechanobiology.
Molecular force sensor development and the study of mechanotransduction are interdisciplinary, and publications in the field often involve teams of researchers from a range of scientific backgrounds. This work is intended to be accessible to advanced undergraduate students and graduate students and should appeal to individuals in the fields of chemistry, physics, engineering, and biology.
Rather than providing an exhaustive list of equations or discussing every chemical and biological method used to describe and develop molecular force sensors, the authors include the principles most relevant to developing molecular force sensors and highlight some of the key literature demonstrating the use of such sensors in laboratory settings.
This book is coming soon. In the meantime, please contact your library or ACS sales representative for purchase options.
Detailed Table of Contents
About the Series
Preface
Biographies
Acknowledgments
Chapter 1
Introduction
1.1
Overview
1.2
Early Discoveries
1.3
Cell Structure and Mechanotransduction
1.4
How Do Cells Translate between the Language of Mechanics and the Language of Chemistry?
1.5
Where do Forces Originate?
1.6
Insider Q&A: Carsten Grashoff
1.7
Evolution of Molecular Sensors
1.8
That’s a Wrap
1.9
Read These Next
Chapter 2
Using Molecules as “Springs”: Force–Extension Behavior of Macromolecules
2.1
Overview
2.2
Extension and Energy
2.3
Modeling Polymer Behavior: Force–Extension Graphs
2.4
Types of Polymer Force–Extension Behavior
2.5
Models of Polymer Extension
2.5.1
Ideal Chain
2.5.2
Worm-like Chain
2.6
Molecular Springs with Secondary Structure
2.7
Insider Q&A: Carsten Grashoff
2.8
How Forces Influence the Kinetics and Thermodynamics of Unfolding
2.9
That’s a Wrap
2.10
Read These Next
Chapter 3
Förster Resonance Energy Transfer (FRET)
3.1
Introduction
3.2
Overview
3.3
History of FRET
3.4
Basis for FRET
3.5
Effect of Distance on FRET
3.6
Selecting FRET Pairs
3.7
Calibrating Molecular Tension Sensors
3.8
Measuring FRET Efficiency
3.8.1
Donor-Intensity-Based FRET
3.8.2
Acceptor Bleaching
3.8.3
Sensitized Emission
3.8.4
Spectral Imaging
3.8.5
Fluorescence Lifetime Imaging Microscopy (FLIM)
3.9
That’s a Wrap
3.10
Read These Next
Chapter 4
Genetically Encoded Tension Sensors
4.1
Overview
4.2
Designing a Genetically Encoded Tension Sensor
4.3
Insider Q&A: Wendy Gordon
4.4
Types of Genetically Encoded Tension Sensors
4.4.1
Stretch-Sensitive FRET (stFRET)
4.4.2
Spectrin stFRET (sstFRET)
4.4.3
PRIM-Based Strain Sensor Module (PriSSM)
4.4.4
Tension Sensor Module (TSMod)
4.4.5
Challenges of Using TSMod Sensors
4.4.6
Circularly Permutated stFRET (cpstFRET)
4.5
Progress and Outlook
4.6
Insider Q&A: Brenton D. Hoffman
4.7
That’s a Wrap
4.8
Read These Next
Chapter 5
Synthetic Tension Sensors
5.1
Introduction
5.2
Insider Q&A: Xuefeng Wang
5.3
Types of Tension Sensors: Analog
5.3.1
Molecular Tension Force Microscopy (MTFM) Sensors
5.3.2
Polypeptide-Based Sensors
5.4
Types of Tension Sensors: Digital
5.4.1
Protein-Based Sensors
5.4.2
Nucleic Acid-Based Sensors
5.4.2.1
DNA Hairpin Sensors
5.4.2.2
DNA Hairpins Synthesized as Single Oligonucleotides
5.4.2.3
DNA Tension Sensors Tethered to Fluid Interfaces
5.4.2.4
Other Hairpin Sensor Derivatives: Gold Nanoparticle Tension Sensor to Improve S/N
5.4.2.5
Transient Force Detection
5.4.2.6
DNA Rupture Sensors
5.4.2.7
Reversible Sensors that Measure Forces Greater Than 19 pN
5.5
Insider Q&A: Mingxu You
5.6
Progress and Outlook/Conclusions
5.7
That’s a Wrap
5.8
Read These Next
Chapter 6
Readout Methods
6.1
Introduction
6.2
Microscopy-Based Methods
6.2.1
Intensity
6.2.2
Ratiometric
6.2.3
Lifetime
6.2.4
Polarization to Determine Orientation
6.2.5
Super-Resolution Microscopy
6.2.6
Multivalent Tension Sensors
6.3
Nonmicroscopy-Based Methods
6.3.1
Flow
6.3.2
Catalytic Amplification
6.3.3
TGF-B Aptamer
6.4
Conclusions
6.5
That’s a Wrap
6.6
Read These Next
Chapter 7
Future Outlook
7.1
Overview
7.2
Future Outlook
7.3
Insider Q&A: Young-Wook Jun
7.4
Insider Q&A: Alex Dunn
7.5
That’s a Wrap
7.6
Read These Next
Chapter 8
Check Your Understanding
Bibliography
Glossary
Index
Reviewer quotes
I would recommend this book to any student or researcher who is interested in ways that biology and physics can be married together. These are two fields not often associated together, so someone with experience in one or the other would benefit greatly from reading this.
Rachel Bender earned her B.A. in chemistry and biochemistry from Capital University in Columbus, Ohio in 2017 before beginning her graduate studies in the Department of Chemistry at Emory University. She is currently developing new sensors for measuring molecular forces in cells and studying the relationship between force sensing and a cell’s biological response. She has also been recognized with a NSF Graduate Research Fellowship Program Honorable Mention. She is passionate about bridging the gap between scientists and the general population and has worked with the Atlanta Science Festival and the Atlanta Discovery Program to share scientific research and concepts with both children and adults. Outside of research, she spends her time playing the cello and is an avid chamber musician as well as a member of the Atlanta Community Symphony Orchestra and the Gwinnett Symphony and Northeast Atlanta Ballet Orchestras.
Khalid Salaita is a Professor of Chemistry at Emory University in Atlanta, Georgia (USA). Khalid grew up in Jordan and moved to the US in 1997 to pursue his undergraduate studies at Old Dominion University in Norfolk, Virginia (USA). He worked under the mentorship of Prof. Nancy Xu studying the spectroscopic properties of plasmonic nanoparticles. He then obtained his Ph.D. with Prof. Chad Mirkin at Northwestern University (Evanston, Illinois, USA) in 2006. During that time, he studied the electrochemical properties of organic adsorbates patterned onto gold films and developed massively parallel scanning probe lithography approaches. From 2006-2009, Khalid was a postdoctoral scholar with Prof. Jay T. Groves at the University of California at Berkeley (USA) where he investigated the role of receptor clustering in modulating cell signaling. In 2009, Khalid started his own lab at Emory University, where he investigates the interface between living systems and engineered nanoscale materials. To achieve this goal, his group has pioneered the development of molecular force sensors, DNA mechanotechnology, smart therapeutics, and nanoscale mechanical actuators to manipulate living cells. In recognition of his independent work, Khalid has received a number of awards, most notably: the Alfred P. Sloan Research Fellowship, the Camille-Dreyfus Teacher Scholar award, the National Science Foundation Early CAREER award, and the Kavli Fellowship. Khalid is currently a member of the Enabling Bioanalytical and Imaging Technologies (EBIT) study Section and an Associate Editor of Smart Materials. Khalid’s program has been supported by NSF, NIH, and DARPA.
