1 of 53

Diffusion as Biology's Null�Hypothesis for Dynamics

Quantitative Biology Bootcamp

Fall 2026

2 of 53

Adventure Map

a physical view

of biological phenomena

(for your rotations

and your PhD project)

physical

models

order-of-magnitude

estimates

pen-and-paper

calculations

numerical

simulations

in Python

theory —

experiment

dialogue

Math and

computation

as biology’s

next microscope

the power

of abstraction

biological

numeracy

statistical

analysis

3 of 53

Physical Approaches Allow Us to Formalize Our Null Hypotheses

4 of 53

We Will Examine Diffusion as Biology’s Null Hypothesis for Molecular Dynamics

5 of 53

Time Scales in Biology and�Usain Bolt

6 of 53

False Starts and Olympic Runners

Wikipedia

Lipps et al. (2011)

7 of 53

But This Might Not Be That Fair!

8 of 53

Time Scales of Information Transfer in Neurons

  • What are the time scales of these processes?

9 of 53

Electrical Impulse Propagation in Unmyelinated Neurons

Hochbaum et al. (2014)

10 of 53

Electrical Impulse Propagation in Unmyelinated Neurons

  • Note that propagation in myelinated neurons is ~100 m/s

Hochbaum et al. (2014)

Cell Biology by the Numbers

11 of 53

Axonal transport of cellular components

  • Is this fast or slow?

Droz and Leblond (1962)

12 of 53

Passive vs Active Transport in the Neuron

13 of 53

Fourier Takes Stuff(t) Beyond Mechanics - New Concepts Everywhere

14 of 53

Look at the Ambition

15 of 53

Look at the Ambition

16 of 53

Look at the Ambition

17 of 53

We Will Examine Diffusion as Biology’s Null Hypothesis for Molecular Dynamics

18 of 53

Robert Brown and the Discovery of Brownian Motion

Jean Perrin

19 of 53

How Long Does it Take for a Molecule to Diffuse a Distance x?

20 of 53

Thermal Fluctuations Drive Diffusion

21 of 53

The Concept of the Field Revolutionized Physics

22 of 53

The Field Concept�Concentration Field

23 of 53

A Constitutive Model for Diffusive Transport

24 of 53

Fick’s Law and the Units of the Diffusion Coefficient

25 of 53

Using Dimensional Analysis to Estimate the Time Scale for Diffusion

26 of 53

Diffusion times

  • Diffusion time for a protein in water (100 μm2/s)

27 of 53

Stroboscopic Illumination to Track Diffusing Molecules in E. coli

English et al. (2011)

28 of 53

Your Turn: Estimate the Diffusion Coefficient of GFP in E. coli

English et al. (2011)

29 of 53

Diffusion constants vary greatly in biology

30 of 53

Diffusion constants depend on the molecular size and environment

31 of 53

Axonal transport of cellular components

  • Is this fast or slow?
  • Could this be diffusion?

Droz and Leblond (1962)

32 of 53

Watching axonal transport in real time

  • What’s the speed of protein movement?

Cui et al., J. PNAS 104:13666 (2007)

33 of 53

Active or Passive?�Vastly Different Time Scales in Axonal Transport

Morfini et al. (2011)

34 of 53

Beating the Diffusion Speed Limit

  • Impossibly long time scales associated with diffusion over large distances
  • Nature’s solution: active transport

35 of 53

Time Scales of Information Transfer in Neurons

  • What are the time scales of these processes?

36 of 53

Diffusion at the Synapse

37 of 53

Your Turn: Estimate the Current Flowing Through a Potassium (Ion) Channel

38 of 53

Single Ion-Channel Current Measurements

39 of 53

Calculating the Temporal Evolution of the Concentration Profile

40 of 53

Three Different Ways of Solving the Diffusion Equation

41 of 53

Jean Perrin Measurements�Early 20th Century

42 of 53

Measuring One-Dimensional Diffusion of a Molecular Motor on a Microtubule

Joe Howard

43 of 53

Diffusion and the Random Walk

44 of 53

Stochastic and Probabilistic Views of Diffusion

45 of 53

Diffusion and the Random Walk

46 of 53

Diffusion by Coin Flips

47 of 53

A Random Walk in 2D

  • We can simulate this in Python!

48 of 53

Three Different Ways of Solving the Diffusion Equation

49 of 53

Our Second Key Equation�The Diffusion Equation

50 of 53

Adventure Map

a physical view

of biological phenomena

(for your rotations

and your PhD project)

physical

models

order-of-magnitude

estimates

pen-and-paper

calculations

numerical

simulations

in Python

theory —

experiment

dialogue

Math and

computation

as biology’s

next microscope

the power

of abstraction

biological

numeracy

statistical

analysis

51 of 53

The Power of Abstraction�The Map Is Not the Territory

52 of 53

One Person’s Mechanism Is Another Persons’s Coarse Grained Model

to understand a phenomenon you don’t need to know where the molecules are!

53 of 53

SLIDE LEFT BLANK INTENTIONALLY