Biophysics

Eva-Maria S. Collins

University of California, San Diego

Hands-on Research Complex Systems School ICTP, Trieste, 2013

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What is biophysics?

“I’m starting to do some homework for places that might be good to apply for graduate school, but am looking for a bit more information about certain fields. I’ve been working at a computational physical chemistry/biophysics lab for a little under 2 years now, but we exclusively focus on the size of proteins so that’s all I really know. I am curious what else does the field of biophysics have to offer. Would you have time to meet and talk to me about different avenues in biophysics, and in specific about what you do?”

email by UCSD Physics undergrad

What is biophysics? “The branch of biology that applies the methods of physics to the study of biological structures and processes.“

“A branch of science concerned with the application of physical principles and methods to biological problems.”

“Biophysics is a bridge between biology and physics.” (Biophysical society)

Study & understanding of physical aspects of the living world

“All of Biology is Fair Game” (Biophysical society website)

What do biophysicists study?

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Biophysics spans many scales

Biophysics spans many scales DNA dynamics

movie: web

Biophysics spans many scales Molecular Motors

kinesin motor walking on microtubule filament movie: web

Biophysics spans many scales Cell migration (Erin Rericha)

Fish keratocyte movie: S. T. Norrelykke

Dictyostelium movie: Firtel lab

Biophysics spans many scales Cell aggregates, tissues

Embryonic fish cells and tissues

Biophysics spans many scales Organisms (flatworm lab)

Flatworm asexual reproduction

Regenerating hydra

Biophysics spans many scales Flocking

movie: web

Biophysics in the Collins Lab

Biomechanics Regeneration

Asexual reproduction, evolution & aging

Neurogenesis & Learning

Biophysics in the Collins Lab

Princeton University:

Sofia Quinodoz Michael Thomas Jared Talbot Keith Mickolajczyk

UC San Diego: Olivier Cochet-Escartin My Du Dang Robert Schwartz Jason Carter

mesoderm Cyclops mRNA

ectoderm Lefty mRNA MZoep mutant

Tissues that interact in early

embryonic development: mesoderm and ectoderm

Role of mechanics for development

Big questions

• Can we understand movements in terms of a physical interaction between two different materials?

• How can we relate macroscopic tissue properties to the properties of the individual cells? And thus modify them using molecular biology techniques?

Molecular determinants of tissue surface tension see: Manning, Foty, Steinberg & EMS, PNAS 107 (2010)

Molecular determinants of tissue surface tension see: Manning, Foty, Steinberg & EMS, PNAS 107 (2010)

Silly Putty

Tissue behavior is time dependent -

viscoelastic ( Eric Weeks)

rounding behavior is driven by surface tension ( Charles Boudin)

Surface Tension σ

air-liquid interface

[σ ] = erg/cm2 = dyne/cm

cell-medium interface

subunits mobility Cohesion

liquids molecules Brownian

motion

van-der-Waals forces

tissues cells Active motion adhesion molecules, cell

processes

Difference in energy ( W) between a surface cell

and an interior cell, times the number of cells per unit surface area

Surface tension drives rounding and fusion of liquid drops and embryonic tissues

EMS et al., HFSPJ (2008)

olive oil droplets cell aggregates (~10^5 cells each)

If fluid-like: Cell migration should be diffusive

wikipedia.org

Mean squared displacement

If fluid-like: Cell migration should be diffusive

3D tracking in coll. with T. Bacarian, M.L. Manning

~ tMSD

Diffusion constant:

D = 0.4 ± 0.1µm2/min

Diffusion:

PasrD

Tk01.0

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Naively with Stokes-Einstein:

Cell migration is an active process!

Cell migration is a low Reynolds number motion

Stokes drag:

Einstein relation:

6 )( tDtMSD Diffusion: Reynolds number:

Immiscible fluids arrange themselves according to their surface tensions

Liquid with lower surface tension spreads on liquid with

higher surface tension

surface tension (water) ~ 72 dyne/cm surface tension (oil) ~ 18 dyne/cm

Immiscible tissues arrange themselves according to their surface tensions, too

EMS et al., HFSPJ (2008)

Techniques to quantify surface tension

Pendant drop

Apply known force change in geometry as readout

gravity

Apply known geometry change in force as readout

F= 0

F= F0

Parallel plates

Guevorkian et al., PRL 104 (2010) Foty et al., Dev. 122 (1996) EMS et al., HFSPJ (2008)

Surface tension governs cell arrangement

EMS et al., HFSPJ (2008)

Manning, Foty, Steinberg & EMS, PNAS 107 (2010)

Cancer: Tissue surface tension as indicator for malignancy

Hegedus et al., Biophys J (2006) Winters et al., Int. J. Cancer (2005) Fritsch, Nature Physics (2010) Basan et al., (2010)

Collagen invasion assay

σ

Drug therapies: effects on adhesion and tension important

Flatworms (planarians)

Planarians: Masters of regeneration

1 week later

cut

Rescue 30% stem cells

Wagner et al., Science 2011

Morgan (1910)

F. Cebrià, (2007)

~ 10,000 neurons

Crazy regenerative powers complexity

Asexual reproduction in planarians

Mechanics: how do they do it? Statistics: Reproduction strategy, time scales Evolution: How create diversity? Aging: Immortal because asexual? http://whitbytech.edu.glogster.com/ms

perry-planaria-p2/

image sequence: B. Lincoln

Experiment : ~ 5yrs; > 11,000 divisions

5 families (individuals)

Experiment : > 5 years; > 11,000 divisions

Thomas & EMS, J Exp Biol 214 (2011) FREE!

Reproduction Waiting Time distributions

www.oum.ox.ac.uk

Reproduction dynamics

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Asexual reproduction dynamics

What determines the time it takes for a worm to divide?

It matters who your parent was

Dunkel, Talbot &EMS (Phys. Biol. 8, 2011)

It matters how big you were at birth

Thomas, Quinodoz & EMS (J. Stat. Phys, in print)

Worms “born” bigger divide faster

Area at division and area at birth are uncorrelated

faster

Area at division determines the number of offspring

k=1

k=2

k=3

see also: Quinodoz, Thomas, Dunkel & EMS (J. Stat. Phys. ,2011)

Worms grow bigger before dividing and making more offspring, i.e. no real tradeoff between size and number

Thomas, Quinodoz & EMS (J. Stat. Phys, in print)

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Time scales for planarian experiments are very long

Regeneration: 1-2 weeks Asexual reproduction: months/years NOT GOOD FOR DOING EXPERIMENTS IN THIS SCHOOL!

We study worm behavior instead!

movie: web

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In the lab: Planarian locomotion

cilia-driven

musculature-driven

Keith Mickolajczyk, Olivier Cochet-Escartin

image analysis ImageJ+Octave (free!) Matlab

When stressed (cut), planarians start to “loop”

Keith Mickolajczyk, Olivier Cochet-Escartin

FFT

Looping is supposed to be an “escape behavior”

Question: Which one is faster: Looping or gliding?

Gliding frequency: fg = 1/T T: time to displace one body length

Looping frequency: fl = 1/T

Looping may be caused by intermittent lack of neurotransmitter

Keith Mickolajczyk, Olivier Cochet-Escartin movie: Olivier C.E.

Flatworms are awesome