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How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli 1 , Luis Alvarez 1 , Benjamin M. Friedrich 2 , Laurence G. Wilson 3 1 CAESAR, Bonn 2 Max Planck Institute for the Physics of Complex Systems 3 University of York, Department of Physics
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Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Jul 28, 2018

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Page 1: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

How do sperm find the egg? Cross-fertilization of

theory and experiment

Jan F. Jikeli1, Luis Alvarez1, Benjamin M. Friedrich2, Laurence G. Wilson3 1 CAESAR, Bonn 2 Max Planck Institute for the Physics of Complex Systems 3 University of York, Department of Physics

Page 2: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

How do sperm find the egg?

Page 3: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

The search environment matters

Internal fertilization

© Eisenbach lab

Page 4: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

The search environment matters

© Rene Pascal, CAESAR

10 cm

100 mm

Internal fertilization

External fertilization

© Eisenbach lab

Page 5: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Idealization: sperm path are persistent random walks

Friedrich et al.: Physical Biology (2008)

Page 6: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Given an initial target distance R0 and finite search time ts, there is an optimal persistence length lp*

Search along persistent random walks

Friedrich et al.: Physical Biology (2008)

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Autonomous motility control

[Kaupp et al. 2005]

XXX

motility

sensing

© Rene Pascal, CAESAR

Close to the egg, there is true navigation

Page 8: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

The egg releases chemical guidance cues

Page 9: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Theory: Sperm from marine species steer along helical paths

Friedrich et al.: PNAS (2007) Friedrich et al.: NJP (2008) Friedrich et al.: PRL (2009)

Page 10: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Measuring concentration = Counting molecules

Concentration sensing is subject to strong shot noise

time

detecting single molecules

Page 11: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

We showed that navigation is adapted to tolerate noise

noise-free steering response

response to signaling noise

noise-induced drift

Page 12: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

How to measure a gradient?

exploitation exploration

Page 13: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Gradient sensing strategies are adapted to noise level

Alvarez, Friedrich, Gompper, Kaupp: Trends Cell Biol. (2014) Berg, Purcell: BPJ (1977)

Page 14: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Tiny bacteria can keep their direction only for a few seconds

Page 15: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Slow slime molds have sufficient time for spatial comparison

Berg, Purcell: BPJ (1977)

signal-to-noise ratio

Page 16: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Navigation strategies of cells are adapted to noise level

Alvarez, Friedrich, Gompper, Kaupp: Trends Cell Biol. (2014) Berg, Purcell: BPJ (1977)

Page 17: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Let’s consider the simpler 2d case

How does steering along circular paths work?

Page 18: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Sperm swim along circular paths close to boundaries

BMF, I Riedel-Kruse, J Howard, F Jülicher, J exp Biol 213, 2010

Page 19: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Theory: Sperm measure concentration along circular paths

Page 20: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

concentration stimulus

Theory: Sperm measure concentration along circular paths

swimming path

Page 21: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

concentration stimulus

A signalling system transfers the stimulus into steering

50 µm

swimming path

path curvature

minimal description

as adaptation module

signalling system

inside sperm flagellum

Page 22: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Stimulus oscillations elicit curvature oscillations

swimming path

concentration stimulus path curvature

Page 23: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Theory of sperm chemotaxis

Friedrich, Jülicher: PNAS (2007)

Page 24: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Sperm measure concentration

along circular paths and dynamically

adjust their beat

in a precisely timed manner

Page 25: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

2D

3D

Theory

Page 26: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Steering feedback aligns helical paths with the gradient

Friedrich, Jülicher: PNAS (2007)

Page 27: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

How to test the theory?

Page 28: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

3D-tracking from 2D-holographic images

z

y

x 2D-diffraction pattern

coherent laser light

Page 29: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Numerical reconstruction of 3D-light beam

z

y

x

Rayleigh Sommerfeld back-propagator

2D-diffraction pattern

Page 30: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Sperm swim along helical paths

Jikeli*, Alvarez*, Friedrich*, …, Kaupp: Nature Comm 6, 2015 (*=equal contribution)

Page 31: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

How do sperm steer along helical paths?

Page 32: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Using light to “print” 3D concentration gradients

Chemoattractant with chemical cage UV light removes cage

Page 33: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Using light to “print” 3D concentration profiles

Page 34: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

We compute how the concentration evolves in time

calibrated light intensity quantum yield diffusion coefficient

Page 35: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Tracking a sperm cell in a 3D concentration profiles

UB Kaupp

Page 36: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Helical paths bend in the direction of the local gradient

Jikeli*, Alvarez*, Friedrich*, …, Kaupp: Nature Comm 6, 2015

Page 37: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

We can extract the sensory-motor transfer function

Phase-locked oscillations with phase-lag of 167°±35°, close to the optimum value 180°

Cross-correlation

stimulus path curvature

Page 38: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Theory and experiment of helical steering

swimming path

concentration stimulus path curvature

Page 39: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Experiments prompt an extension of the theory

Small-amplitude oscillations of flagellar asymmetry

gradual helix alignment

Page 40: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Experiments prompt an extension of the theory

Small-amplitude oscillations of flagellar asymmetry

gradual helix alignment

Large amplitude modulations of flagellar asymmetry

sharp turns

Page 41: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Sharp turns are used in emergencies

Experiment

Jikeli*, Alvarez*, Friedrich*, …, Kaupp: Nature Comm 6, 2015

Page 42: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Experiment and theory of adaptive feedback

Experiment Theory

Page 43: Cross-fertilization of theory and experimentasg_2015/asg_fwm1/fw1talks/... · How do sperm find the egg? Cross-fertilization of theory and experiment Jan F. Jikeli1, Luis Alvarez1,

Thank you for your attention !

The experimental team Jan Jikely Luis Alvarez Laurence Wilson

René Pascal Rèmy Colin Magdalena Pichlo Andreas Rennhack Christopher Brenker

U Benjamin Kaupp