Studying the Relationship Between Cellular Mechanics and Metabolism Open Access

Abstract

Mechano-transduction plays a key role in modulating cellular processes, especially in cancer cells. Past studies have illustrated that mechanical inhibition can modulate the activity of metabolic pathways, while inhibition of glycolysis and other processes can attenuate cellular mechanical activity. However, past studies fail to study the relationship between metabolism and single-molecule traction forces that occur on a pN scale. In this work, we aimed to discover the relationship between metabolism and pN traction forces by synthesizing tension gauge tether (TGT) probes, plating cells on 12 pN and 56 pN tension probes, and finally by inhibiting mechanical and metabolic activity through the use of mechanical inhibitors, blebbistatin and Y27632, and metabolic inhibitors, 2-deoxy-D-glucose (2DG) and 6-aminonicotinamide (6AN.) In summary, we discovered that TGT probes modulate ATP levels in HeLa and MEF cells, inhibition of traction forces lowers ATP levels, and blocking glycolysis and PPP leads to decreases in ATP levels. Future works could utilize DNA tension probes to study other cancer cells lines. 

Table of Contents

Introduction ……………………………………………………………………………………………………………………………. 1

Methods  …………………………………………………………………………………………………………………………………. 9

Results and Discussion …………………………………………………………………………………………………………... 12

Conclusion and Future Directions ………………………………………………………………………………………….. 26 

Supplemental Data ……………………………………………………………………………………………...................... 27

References  ……………………………………………………………………………………………………………………………. 28

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Chemistry, Biochemistry
Keyword	Tension Probes TGT DNA
Committee Chair / Thesis Advisor	Khalid Salaita, Emory University
Committee Members	Malathy Shanmugam, Emory University Antonio Brathwaite, Emory University

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