Hands-on Research Complex Systems School
ICTP, Trieste, 2013
Biophysics
Eva-Maria S. Collins
University of California, San Diego
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?”
2
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
What do biophysicists
study?
“All of Biology is Fair Game”
(Biophysical society website)
Biophysics spans many
scales
6
Biophysics
DNA spans
dynamics
many scales
movie: web
Biophysics
Molecular
spans
Motors
many scales
kinesin motor walking on microtubule filament
movie: web
Cell
Biophysics
migration
spans
(Erinmany
Rericha)
scales
Fish keratocyte
movie: S. T. Norrelykke
Dictyostelium
movie: Firtel lab
Biophysics
Cell aggregates,
spans many
tissues
scales
Embryonic fish cells and tissues
Biophysics
Organismsspans
(flatworm
manylab)
scales
Regenerating hydra
Flatworm asexual
reproduction
Biophysics
Flocking
spans many scales
movie: web
Biophysics in the Collins Lab
Biomechanics
Regeneration
Asexual reproduction,
evolution & aging
Neurogenesis &
Learning
Biophysics in the Collins Lab
Princeton University:
UC San Diego:
Sofia Quinodoz
Michael Thomas
Jared Talbot
Keith Mickolajczyk
Olivier Cochet-Escartin
My Du Dang
Robert Schwartz
Jason Carter
Role of mechanics for development
mesoderm
ectoderm
Cyclops mRNA
Lefty mRNA
Tissues that interact in early
embryonic development:
mesoderm and ectoderm
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
tissuedependent
surface tension
Tissue determinants
behavior isoftime
see: Manning, Foty, Steinberg & EMS, PNAS 107 (2010)
viscoelastic ( Eric Weeks)
Silly
Putty
rounding behavior is driven by surface tension
( Charles Boudin)
Surface Tension σ
Difference in energy ( W) between a surface cell
and an interior cell, times the number of cells per unit
surface area
2
[σ ] = erg/cm = dyne/cm
air-liquid interface
subunits
mobility
cell-medium interface
Cohesion
liquids
molecules Brownian
motion
van-der-Waals forces
tissues
cells
adhesion molecules, cell
processes
Active motion
Surface tension drives rounding and fusion of
liquid drops and embryonic tissues
olive oil droplets
EMS et al., HFSPJ (2008)
cell aggregates
(~10^5 cells each)
If fluid-like: Cell migration should be diffusive
Mean squared displacement
wikipedia.org
If fluid-like: Cell migration should be diffusive
MSD ~ t
Diffusion:
Diffusion constant:
D = 0.4 ± 0.1µm2/min
3D tracking in coll. with T. Bacarian, M.L. Manning

Cell migration is a low Reynolds number motion
Reynolds number:
Diffusion: MSD (t )  6D t
Einstein relation:
Stokes drag:
 Naively with Stokes-Einstein:

kT
D6r
 0.01Pas
Cell migration is an active process!
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
Apply known force
Apply known geometry
 change in geometry
as readout
 change in force as readout
F= 0
gravity
F= F0
Pendant drop
Guevorkian et al., PRL 104 (2010)
Parallel plates
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
Drug therapies: effects on adhesion and tension important
Collagen invasion assay
Hegedus et al., Biophys J (2006)
Winters et al., Int. J. Cancer (2005)
Fritsch, Nature Physics (2010)
Basan et al., (2010)
σ
Flatworms (planarians)
Planarians: Masters of regeneration
cut
Morgan (1910)
1 week later
30% stem cells
Rescue
Wagner et al., Science 2011
Crazy regenerative powers  complexity
F. Cebrià, (2007)
~ 10,000 neurons
Asexual reproduction in planarians
Mechanics: how do they do it?
Statistics: Reproduction strategy, time scales
Evolution: How create diversity?
http://whitbytech.edu.glogster.com/ms
perry-planaria-p2/
image sequence: B. Lincoln
Aging: Immortal because asexual?
Experiment
Experiment: >: ~5 5yrs;
years;> >11,000
11,000divisions
divisions
5 families (individuals)
Thomas & EMS, J Exp Biol 214 (2011)
FREE!
Reproduction
Waiting Time
distributions
Reproduction
dynamics
www.oum.ox.ac.uk
Asexual reproduction dynamics
What determines the time it takes for a worm to divide?
35
It matters who your parent was
Dunkel, Talbot &EMS (Phys. Biol. 8, 2011)
It matters how big you were at birth
Worms “born” bigger divide faster
faster
Area at division and area at birth are
uncorrelated
Thomas, Quinodoz & EMS (J. Stat. Phys, in print)
Area at division determines the number of offspring
k=1
k=2
k=3
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)
see also: Quinodoz, Thomas, Dunkel & EMS (J. Stat. Phys. ,2011)
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
39
In the lab: Planarian locomotion
cilia-driven
musculature-driven
Keith Mickolajczyk, Olivier Cochet-Escartin
40
When stressed (cut), planarians start to “loop”
image analysis
ImageJ+Octave (free!)
Matlab
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