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
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