# Presentation: 833734

## Entropic Forces in Single-Biomolecule Mechanics Philip Nelson, University of Pennsylvania, DMR-0404674

- Entropic Forces in Single-Biomolecule Mechanics Philip Nelson, University of Pennsylvania, DMR-0404674

***Spare the Rod:******            ***1. Intellectual merit
- The DNA in our cells must not only store genetic information: It must constantly engage in mechanical rearrangements in the course being read, duplicated, and so on. Recent advances in the imaging and manipulation of single molecules seemed to show that a very simple mathematical model of DNA mechanics -- the *“Elastic rod”* model -- could describe its behavior very well. But the elastic rod picture seemed to rule out the very tightly-bent shapes that we know DNA frequently  assumes in cells.
- We imaged DNA using atomic force microscopy (above), obtaining unprecedented resolution (closeup below). We found that on the nanometer scale, relevant in cellular processes, DNA is much more flexible than had been predicted by the elastic rod model. [Images from PA Wiggins, T van der Heijden,  F Moreno--Herrero, A Spakowitz, R Phillips, J Widom, C Dekker and PC Nelson, Nature Nanotechnology, in press.]
- Our discovery of this unexpected, and biologically important, behavior of DNA relied on a tight interplay of theory and experiment, and illustrates the unity of scientific concepts. Ideas borrowed from renormalization-group theory (initially developed for the study of phase transitions) were crucial for initially formulating our hypothesis, and for the method we proposed to our experimental colleagues to test the hypothesis.

- Besides being technically successful, our new model of DNA mechanics is mathematically very simple. This simplicity will make it a *practical* tool for explaining known DNA behavior, and for predicting new phenomena.

**Notes:**
FURTHER REMARKS
Theorists view their job as seeking simplicity wherever it can legitimately be found, and in this we succeeded. Generally, when we find a prevailing theory (elastic rod model) that breaks down when examined in a new regime (few-nanometer length scales), it’s necessary to replace it by a more complicated theory that embraces the old and the new results. In contrast, our new model is just as simple as elastic-rod, despite its larger domain of validity. Other, more  complicated models exist, but we wanted one that real experimenters in the trenches could use for themselves.
Theorists also seek to apply concepts discovered in one realm of science (here phase transitions) to other, seemingly distant, fields (here DNA in its fluctuating nanoworld). Our work illustrates the utility of such an approach.
A vast literature, applying engineering-style beam-theory analysis to DNA, will now need to be reconsidered in the light of this discovery.

AUTHOR CONTACT INFO
Paul Wiggins
 * wiggins@wi.mit.edu
 Whitehead Institute
 * Cambridge
 MA 02142
 * United States of America
Work Telephone 1 617-324-2342

Thijn van der Heijden
 * heijden@mb.tn.tudelft.nl
 Delft University
 Kavli Institute of Nanoscience
 Lorentzweg 1
 * Delft 2628CJ
 * Netherlands
Work phone  +31 15 2782247 (6 hr later than EST)

Fernando Moreno--Herrero
 * moreno@mb.tn.tudelft.nl
 Delft University
 Kavli Institute of Nanoscience
 Lorentzweg 1
 * Delft 2628CJ
 * Netherlands
Work phone  +31 15 2782247 (6 hr later than EST)

Rob Phillips
 * phillips@pboc.caltech.edu
 Caltech
 Eng Appl Sci
 * Pasadena
 CA
 * United States of America
 91125
Work Phone (626) 395-3374, 818-919-2142

Jonathan Widom
 * j-widom@northwestern.edu
 Northwestern University
Department Biochem., Mol. Biol. & Cell Biol.
 * Evanston
 IL
 * United States of America
 60208
Work phone (847) 467-1887; 224-522-1248

Cees Dekker
 * dekker@mb.tn.tudelft.nl
 Delft University
 Kavli Institute of Nanoscience
 Lorentzweg 1
 * Delft 2628CJ
 * Netherlands
Phone +31 15 2786094(lab);+31 6 3036 2478(cell) 

Philip Nelson
 * nelson@physics.upenn.edu
Univ Pennsylvania
 Physics/Astronomy
 * 209 S 33d St
 * Philadelphia
 PA
 * United States of America
 * 19146
Phone  215-898-7001
URL www.physics.upenn.edu/~pcn

## Entropic Forces in Single-Biomolecule Mechanics Philip Nelson, University of Pennsylvania, DMR-0404674

- FURTHER REMARKS
- Theorists view their job as seeking simplicity wherever it can legitimately be found, and in this we succeeded. Generally, when we find a prevailing theory (elastic rod model) that breaks down when examined in a new regime (few-nanometer length scales), it’s necessary to replace it by a more complicated theory that embraces the old and the new results. In contrast, our new model is just as simple as elastic-rod, despite its larger domain of validity. Other, more  complicated models exist, but we wanted one that real experimenters in the trenches could use for themselves.
- Theorists also seek to apply concepts discovered in one realm of science (here phase transitions) to other, seemingly distant, fields (here DNA in its fluctuating nanoworld). Our work illustrates the utility of such an approach.
- A vast literature, applying engineering-style beam-theory analysis to DNA, will now need to be reconsidered in the light of this discovery.
- AUTHOR CONTACT INFO
- Paul Wiggins
-  * wiggins@wi.mit.edu
-  Whitehead Institute
-  * Cambridge
-  MA 02142
-  * United States of America
- Work Telephone 1 617-324-2342

## Entropic Forces in Single-Biomolecule Mechanics Philip Nelson, University of Pennsylvania, DMR-0404674

- Thijn van der Heijden
-  * heijden@mb.tn.tudelft.nl
-  Delft University
-  Kavli Institute of Nanoscience
-  Lorentzweg 1
-  * Delft 2628CJ
-  * Netherlands
- Work phone  +31 15 2782247 (6 hr later than EST)
- Fernando Moreno--Herrero
-  * moreno@mb.tn.tudelft.nl
-  Delft University
-  Kavli Institute of Nanoscience
-  Lorentzweg 1
-  * Delft 2628CJ
-  * Netherlands
- Work phone  +31 15 2782247 (6 hr later than EST)

## Entropic Forces in Single-Biomolecule Mechanics Philip Nelson, University of Pennsylvania, DMR-0404674

- Rob Phillips
-  * phillips@pboc.caltech.edu
-  Caltech
-  Eng Appl Sci
-  * Pasadena
-  CA
-  * United States of America
-  91125
- Work Phone (626) 395-3374, 818-919-2142
- Jonathan Widom
-  * j-widom@northwestern.edu
-  Northwestern University
- Department Biochem., Mol. Biol. & Cell Biol.
-  * Evanston
-  IL
-  * United States of America
-  60208
- Work phone (847) 467-1887; 224-522-1248

## Entropic Forces in Single-Biomolecule Mechanics Philip Nelson, University of Pennsylvania, DMR-0404674

- Cees Dekker
-  * dekker@mb.tn.tudelft.nl
-  Delft University
-  Kavli Institute of Nanoscience
-  Lorentzweg 1
-  * Delft 2628CJ
-  * Netherlands
- Phone +31 15 2786094(lab);+31 6 3036 2478(cell)
- Philip Nelson
-  * nelson@physics.upenn.edu
- Univ Pennsylvania
-  Physics/Astronomy
-  * 209 S 33d St
-  * Philadelphia
-  PA
-  * United States of America
-  * 19146
- Phone  215-898-7001
- URL www.physics.upenn.edu/~pcn

## Entropic Forces in Single-Biomolecule Mechanics, Philip Nelson, University of Pennsylvania, DMR-0404674

- A central issue for developmental cell biology is how genes get switched on and off. Biologists have long known that gene switching in some cells, such as bacteria, involves the formation of a loop of DNA. But again, there was a longstanding puzzle of how DNA could readily form loops as tight as the ones seen in living cells. Our work reconciles such observations with single-molecule studies that seemed to point to a very stiff DNA molecule. [Image from Hochschild, Curr Biol 12(2002).]

- Entropic Forces in Single-Biomolecule Mechanics, Philip Nelson, University of Pennsylvania, DMR-0404674

- DNA in our cells spend much of its time assembled into a small “bobbin”  structure (the nucleosome). Our work helps explain the puzzle of how the supposedly DNA molecule -- till now regarded as essentially a very stiff elastic rod -- can easily adopt this tightly bent configuration. [Image from Richmond and Davey, Nature 423 (2003).]

***Spare the Rod           ***2. Broader impact, education, manpower

- Authors Wiggins and Spakowitz were grad students when this work was initiated. van der Heijden is completing his PhD; Moreno is a postdoc. Today Wiggins is a research associate at the Whitehead Institute, Spakowitz is on the engineering faculty at Stanford, and Moreno is heading for a research associate position in Spain.

**Notes:**
Another cultural aspect of impact is strengthening the links between theorists and experimentalists. Indeed, extensive theory-experiment discussions were crucial for this work. A lot of theory has already been done, and a lot of experiments, but they all missed this point about DNA, in part because they were too distant from eath other.